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Home , History of pathology, Samuel Bard (physician), SmILE

Anniversary Issue 1987-2012

Celebrating 25 years of education, clinical service, and research

Dear Colleagues and Friends, among others – and enjoyed the continu- the medical school, university and hospi- Over the years, my wife Vivien and I have ity of those who were here longer than 25 tal for our success. I am delighted that so enjoyed having members of the department years ago and still work with us including many of our friends and supporters from to our home for festive evenings. Years ago, Drs. Perzin, D’Agati, Hibshoosh, Marboe, throughout the Medical Center could be this meant having 25, then 50 and finally Gershon, Axel, Richart and O’Toole and the with us this evening. I am also glad that about 70 to our home in Brooklyn. As the critically important Pat Pringle. The heavy representatives of our sister departments Department of and eventually lifting of the past quarter century has de- have been able to join and would like to the Department of Pathology and Cell Bi- pended almost entirely on those present in personally acknowledge my own mentors ology grew, our home could no longer keep this room tonight. Credit belongs to those and students who are here tonight. up and even division dinners became large. who have gone the distance, those who have It has become clear that “hospital based” come and gone and those who have only For many of you this may be your first ex- departments are also not fêted at Annual recently joined. Each of you has made a dif- posure to the grandeur of Low Library. I Galas at the Waldorf or the Plaza. Thus it ference and it is the contributions of each hope you will have many more chances to became clear that if we were to have a party, of you and all of you that we celebrate this return. Our purpose here is rare – to honor we would have to throw it ourselves. evening. Each , each scientist, each all of us, not just one person, for our work administrator, each student, postdoc and and accomplishment. No funds are being In the past 25 years we have worked togeth- resident has contributed a vital thread to the raised, no books published. We are here er to bring the Department to a new level of fabric of our department. to enjoy each other’s company, to eat, to excellence in clinical service, in scientific re- drink and to dance. search and in education. We have built upon A department does not stand alone. We the base established by those who have gone depend on our colleagues, on the other I raise my glass to all of you before us – Stout, King, Lattes and Murray departments and on the administration of with deepest gratitude. Mike The Accomplishments of the Last 25 Years...

Department of Anatomy & Cell Biology Michael D. Gershon, MD 1767 The Motor Neuron Center co-directors: Migrants fromNYU Drs. Christopher Henderson, Darryl De Vivo Med into Grad Howard Hughes Med- NIH grant revenues Michael Shelanski, Ron Liem, Yuan Chang Studies of enteric nervous system and cell biology and Serge Przedborski are in the foreground. Program initiated to-Grad grant received exceed $30 million Mary Beth Hatton, Lloyd Greene, and In the background are Dr. Lewis Rowland and Michael Shelanski, MD, PhD Carol Mason, Fred Maxfield Patrick Moore former Dean Gerald Fischbach. 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

*Wei Gu Dr. Ron Liem Dr. James restarted Goldman Role of acety

PhD Programs Institute of Discovery of the Discovery of the in Pathobiology Graduate program in T-cell leukemia (HHV8) discovered by Ramon Parsons Professor Richard Axel Kaposi Sarcoma Virus by Adolfo Ferrando BCL6 proto-oncogene by Chang and Moore on Alzheimer’s training grant renewed Riccardo Dalla-Favera lation in p53 regulation PTEN tumor suppressor Taub Institute for Research Discovery and therapeutic New fellowship program in targeting of activated notch Cancer Genetics formed joins Pathology to form the from Oncology Division and the Aging Brain founded Molecular Genetic Pathology Pathology & Cell Biology Motor Neuron Center joins

wins Nobel Prize for studies on olfaction Annual number of tests exceeds 6 million Department of Anatomy & Cell Biology

Department of Pathology & Cell Biology

WHY IS THIS In the year 5738 we were a small and grants us more space. But up the East Side on our way to Bronx and Riverside Drive past Deans David, Tom and Gerry NIGHT DIFFERENT... and young people who sought the heart of Dean Saul hardened Mount Sinai. There we encamp- Dead Dog Park to pitch camp on came and they went. Finally, we refuge from the raging giants of toward us and he gave us gor- ed and entreated and waited. We 168th Street. have entered the Gold(en)man the metropolis of the north and nicht (and bubkes as well). We ate lousy bread that tasted like Age if not the promised land and migrated to the East Side and donned sackcloth and ashes but cardboard and waited longer, but Welcomed by Dean Henrik, we are AIMing HIgher each day. found shelter at NYU. For seven his heart remained hard. the prophecy was false. The bush built labs and the Angel Nih once years our people prospered. Our did not burn, the calf was made again blessed us and our people Thus it has been ordained that numbers increased with stu- So it was that in 5747 (1987 out- of brass, there was no thunder, grew in number and prospered every 25 years the people should dents and postdocs, the chron- side of ), Dean Saul no lightning, no nada and sch- by the work of their hands and gather in a place of celebration lassn sie mutz all over the streets. This was of their minds. And Dean Hen- to retell the tales of our glory, to) ןזָאל ייז ןייג icles were filled with our work said and the NIH rained blessings geh’n) in the language of the East not the promised land; in fact rik was followed by Dean Herb feast and to dance and to drink. upon us. But, in the fullness of Side, and Moishe’s movers came it smelled of ether and carbolic whose rule was a Pardes and for time our labs became cramped and packed the reagents, and the acid – no milk and no honey 10 more years the people were and our students overflowed and freezers and the equipment, and blessed by peace and prosperity. Let us proclaim we beseeched Dean Saul (Shaul the traffic parted and our people, So we journey on across across In the fullness of time Dean Herb “Next Year in HaDean) to loosen our bonds led by Moishe’s moved slowly the wilderness of the Cross left to conquer distant lands and Washington Heights”

2 3 Depend on the Past

1922 Pathology Staff 1906 Arthur Purdy Stout, MD First Virginia Frantz, MD, Cancer 1948-1979 Donald McKay Accession Book Margaret Murray, PhD Arthur Purdy Stout, MD Raffaele Lattes, MD Karl Perzin, MD Chair

1847-1883 Sugical Pathology Alonzo Clark William MacCallum First professor 1883-1893 Chair of Pathology Francis Delafield, MD 1893-1909 P&S Chair of Pathology T. Mitchell Prudden, MD Donald West King 1849 1850 1851 1852 1853 1854 1855 1856 1857 1858 1859 1860 1861 1862 1863 1864 1865 1866 1867 1868 1869 1870 1871 1872 1873 1874 1876 1877 1878 1879 1880 1881 1883 1884 1885 1886 1887 1888 1889 1890 1891 1892 1893 1894 1895 1896 1897 1898 1899 1900 1901 1902 1903 1904 1905 1906 1907 1909 1910 1911 1912 1913 1914 1915 1916 1917 1919 1920 1921 1922 1923 1924 1925 1926 1927 1928 1929 1930 1931 1932 1933 1934 1935 1936 1937 1938 1939 1940 1941 1942 1943 1944 1946 1947 1948 1949 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1961 1962 1963 1964 1965 1966 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1985 1986 1848 1875 1882 1908 1918 1945 1960 1967 1983 1984

First antiseptic First bacteriology Prudden and Affiliation of A. Purdy Stout Construction of John Fenoglio surgery at P&S course taught in others introduce Presbyterian and others current campus Pathology at P&S diphtheria and Hospital serve in Anti-Rh Treatment developed by Freda, Acting Chair tetanus antisera and P&S WWI Gorman and Pollack Many thousands of lives saved! moves (See article by Eldad Hod) from Department of Surgery to Department of Pathology

23rd Street and 4th Avenue 1887-1928 P&S West 59th Street The Early Days of until, after the Civil War, many young studied in Europe, but Prudden worked to buy horses and start to make diphtheria During the interwar and postwar periods, departments and it was not until 1960 that left the United States to study with Robert Koch and brought the science and tetanus vaccines. To get them used, he, perhaps the most important figure was it was unified when Donald McKay became Columbia Pathology in French and German universities and of bacteriology - and the germ theory of dis- Herman Biggs and others started the New Arthur Purdy Stout, one of the founders Chairman. The Department became an Richard H. Kessin, PhD brought them back. ease - to New York. York Board of Health. He wrote many of surgical pathology. A previous history excellent clinical provider, but did not sup- books on pathology and bacteriology, some written by Dr. Raffael Lattes and also pub- port much basic research, until 25 years ago, Reviewing the The Newsletter has done a series of vignettes Prudden was appointed special assistant in with Delafield. It was Prudden, who gave a lished in 1997 contains much information when the power of cell biology and neuro- history of our on important pathologists, including the Pathology at P&S in 1878. It was the first start, in 1906, to Surgical Pathology, which on Dr. Stout and others from that period. science arrived in force, as described by the d e p a r t m e n t early Chairs of our Department. The even full time appointment in Pathology in the has figured so heavily in the Department’s Dr Stout’s autobiography, published in 1997, authors included below. from the 19th earlier Chairs of Anatomy, whose history country. He later reminisced: Finally there history. His biography, available on the web, describes Pathology in the 1930’s and 40’s century could we share, are covered by Mike Gershon in appeared on the horizon in this country a few is worth reading. He retired in 1909 and a and his personal experiences-particularly a lead to a list of the next article. Alonzo Clark (1847-1883) anomalous individuals who cherished the portrait, currently hanging outside Alumni haunting trip through Nazi Germany. names, but in was the first Pathology Professor of whom notion that the science of disease, even in its auditorium, was commissioned by his stu- creating the we have much knowledge. His career etiological and morphological aspects alone, dents and colleagues. Dr. Karl Perzin discusses the period from timeline you see spanned a revolution in includ- was broad and deep enough to command the 1955 to 1987, including Doctors Nathan above and from what I know of 19th cen- ing the germ theory of disease and major exclusive attention of its devotees. The College of Physicians and Surgeons al- Lane, John Fenoglio and Raffaele Lattes. tury biology and medicine (forgive me, I advances in and microscopy, but lied with the Presbyterian Hospital in 1910, This is a story that is too long for the current was a history major), several trends emerge. he is not much remembered. He probably In 1885, at P&S, Prudden taught the first but were not in the same location. The Col- publication, but one that will be continued The first has to do with the emergence of did not have a large department – perhaps American course in bacteriology, funded lege was near the present Roosevelt Hospital on our Website, with a new page dedicated American medicine and science and how only an assistant, according to our archivist by the P&S Club. He had a leading role in and the medical school was across town so to the history of Pathology and the role of closely it followed Europe. Steve Novak. Yet the next Chairs, Francis introducing the germ theory of disease to pathologists had to travel back and forth. It our Department in it. The Lattes history (1856) wrote omnis cellula e cellula – all cells Delafield and T. Mitchell Prudden played an New York and the United States. In 1894 was not until 1928 that the present campus will appear there as well. There are many from preexisting cells – a thought on which enormous role in American medicine and Prudden was attending a medical confer- was built. By that time, another important gaps left here, which the Newsletter will try pathology and cell biology depends. We Public Health. Delafield wrote A Manual ence in Budapest when he learned that horse event had occurred – the arrival of women, to fill in future issues. also depend on the germ theory of disease, of Physical Diagnosis and with his student, antisera against diphtheria toxin could ar- including the extraordinary Dr. Virginia which evolved in the same period. These Prudden, he coauthored A Handbook of rest the course of diphtheria in children. He Kneeland Frantz, as elegantly described by Finally, it is important to note that Pathol- Pathological Anatomy and Histology. Both wired to New York asking his colleagues Heidi Rotterdam later in this booklet. ogy was practiced in a number of clinical A painting of Dr. Lattes by current Pathology ideas penetrated the United States slowly professor Jay Lefkowitch done in the 1970’s

4 5 at Columbia from Genesis to Merger

Michael D. Gershon, M.D.

The histories of biology and medicine actually responsible for his oath is not clear. to see what does not exist on the grounds and very fierce. New York had recently be needed. Because 5 professors, however, Clossy was appointed a Professor of Natu- begin with anatomy. Early ob- Another man with the same name might that the book claims that it exists; it is yet been engaged with the British and French seemed overly expensive, Jay thought that ral Philosophy at King’s College in 1765 served the living machinery with some have written it. The success of rationalism, another to search and find it. The story of in their customary activity, war. Colonial King’s College could start with 3. The fields and established a course in anatomy un- care because it was necessary for them to however, was transient. Both rationalism Vesalius can be understood as a precocious physicians were therefore gaining practice of the new medical school would be anat- der the official countenance of the Presi- do so. Cuisine and faith each required it. as an ideal and observation of anatomical example of a critical anatomical maxim, in the surgical treatment of wounds; more- omy and midwifery, the theory and prac- dent and Board of Governors. This was Whether animals were butchered for food detail were eventually suppressed. Greeks, as valuable to modern cell biologists as to over, the absence of sterile technique, sew- tice of physick, and chemistry and materia the very first course in Anatomy given as or sacrifices were made for gods, it was im- and later Romans, became more concerned early anatomists; it is the principle of Yogi ers, or an adequate supply of clean water medica. On June 23, 1763 the governors of part of the curriculum of any college in portant that practitioners knew, at least in with warfare, conquest, and its moral phil- Berra, “Never can tell what you might see in cities provided an endless supply of sick King’s College approved Jay’s plan in prin- America. Two years after Clossy began to relative terms, what they were doing. The osophical rationalizations than with natu- just by looking”. Vesalius’ enemies may patients. Doctors had to be trained and ciple, but stated that the project could not be “delight” New Yorkers with his anatomi- earliest anatomists were diviners who fore- ral philosophy. Anatomical observation have been after his scalp, but they went a that meant that anatomy, which was the launched until the funds became available. cal lectures, King’s College was petitioned cast the fates of kings and nations from the was condemned in Judeo-Christian tradi- long way toward validating his work. Un- one form of medical knowledge at the time In an age that predated the NIH, Medicare, on August 4, 1767 to launch a real medical shapes of the liver of a ram. That neces- tion because desecrated the hu- fortunately for Vesalius, however, science that was linked to reality, was in demand. and Medicaid, raising funds for teaching school in the winter term. On August 14, sitated a working knowledge of the hepatic man body, which was, the bible maintains, in his day was hard. Peers did not conduct and medicine presented a challenge, but 1767 King’s College decided to comply and location, relations, and gross morphology. created in the likeness of G_d. Egyptians peer reviews, but religious and secular au- Peter Middleton, M.D., who had been it was one that enthusiasm for anatomy one-upped the penurious James Jay by ex- Mummification in Egypt involved consid- agreed, although they thought it was nec- thorities conducted reviews. Vesalius was trained at St. Andrews University of helped to solve. uberantly appointing 6 Professors, which erable dissection of organs and, as early as essary to avoid dissection in order to keep driven to make a pilgrimage to the Holy Dundee, Scotland teamed with a local kept King’s College, at least in respect to 1920 BCE, regulations of what might, with the body fit and trim for life after death. Land, which led, in 1564, to a shipwreck doctor, Samuel Bard (of Hall fame) to give Samuel Clossy, M.D. emigrated to New faculty numbers, competitive with Ed- some charity, be called the medical profes- and his death as a pauper on the island of anatomical demonstrations and lectures York City from Dublin in 1763. Clossy had inburgh. Among the stalwart 6 was Pro- sion appeared in the Code of Hammurabi. Rationalism staged a comeback in the Zakynthos in the Ionian Sea. The death of to interested New Yorkers. They used the trained in medicine at Trinity College in fessor Samuel Clossy, who held down the All of this activity, however, was driven by seventeenth century, beginning in Flan- Vesalius did not end rational anatomical bodies of convicted and executed murder- Dublin and published meticulous works of chair of Anatomy, joining Peter Middleton a belief in gods, capricious demons, and ders, the fields of which became notorious science because a flowering of microscopy ers that they had injected with dye to en- dissection in which he correlated anatomi- in Physiology and Pathology, Samuel Bard the supernatural. for other reasons in 1914-1918. Andreas followed it. able blood vessels to be visualized. These cal findings with disease. The politics of in Physick, John Jones in “Chirugery”, Vesalius was born in Brussels in 1514 into lectures, which evidently were very popu- the hospital at Trinity College, however, John Tennant in Midwifery, and James Nobody who was anybody seems to have a family with a medical tradition. Vesa- Thomas Hooke used the word “cell” in lar, were supplemented by clinical train- drove him out of Dublin. He began teach- Smith, in “Chymistry”, Materia Medica. thought that natural events might be sig- lius acquired an interest in anatomy dur- 1665, describing chambers he observed ing given at the “House of Correction”. It ing in New York at King’s College soon Peter Middleton gave the opening lecture nificant until Thales of Miletus (624 BCE- ing the beginning of his medical educa- in cork. Anton von Leewenhoek pol- is best to keep the morality of that age and after his arrival and he very quickly began on Monday, November 2, 1767, with con- 546 BCE), the man to whom Bertrand tion in Paris, where he was often observed ished lenses of short focal length to get not the current age in mind while consid- to give anatomical lectures. He wrote back siderably more fanfare than is currently Russell attributes the origin of western contemplating bones at the Cemetery of microscopy going and described bacteria ering these historical events. One cringes on August 1, 1764 to a former colleague, our practice. Students, of course, must philosophy, began to do just that in Ionia the Innocents. At that time, barber-sur- and protozoa. These developments were to imagine what constituted clinical train- George Cleghorn, the anatomist who had have attended, but the New York “Mer- (the western coast of what is now Turkey). geons conducted , the practice eventually to transform medicine and ing after the French and Indian War and taught Clossy back at Trinity College, that cury”, which may not have noticed them, Thales introduced “rationalism”, which of which had been revived, but lectur- come to underlie the fields of pathology why the House of Correction was deemed “…You would be amazed with what de- reported that the Board of Governors, all proposed the then novel idea of causality, ers directed the dissections and students and cell biology; however, they affected a suitable place for it to occur. In any case, light…” his lectures were received (this de- of the professors, the president of the col- a concept that had not previously colored watched. The goal of the exercise was not virtually nothing in New York on June 10, while these activities were in full sway, an light has passed on through multiple suc- lege, members of the Supreme Court in the reasoning of ancient minds. Under to observe and describe what one saw, but 1760 when the first law regulating medi- impressed James Jay, the older brother of cessors to Paulette Bernd today). full robes and regalia, as well as his “Ex- rationalism, events were attributed to a to find what , the ancient Roman, had cine was passed in this city. On that day, John Jay (who was to graduate with a de- cellency, the Governor, Sir Henry Moore”, natural , whether or not that cause written should be seen. A problem, unsus- a certain Cadwalder Colden, a physician gree in law from New York’s King’s College were all present to hear, and presumably was known or understood; moreover, a pected prior to Vesalius, was that faith in who was repeatedly elected the Lieuten- and become first Chief Justice of the United learn, about the history of the “…ancient particular cause was thought to repro- Galen, which was absolute, had been mis- ant Governor of the New York province States Supreme Court) took it upon himself and present state of medicine”. Clossy fol- ducibly produce the event to which it was placed. Human dissection was forbidden (colony), pushed through a law that stated to medically improve the colony. Jay, who lowed Middleton in the afternoon and in- linked without change by the intervention in ancient Rome, so Galen worked and that: “No person whatsoever shall practice was a physician who had been trained in troduced the human body. King’s was the of a capricious will. To rationalists, there described Barbary apes, which he thought as a physician or surgeon …before he shall Edinburgh, went abroad in 1762 to raise second medical school to be established in was a law that governs the universe, but it were close enough (perhaps a precocious first be examined in physick or surgery funds and lift the profile of King’s Col- colonial America but it worked quickly; was a natural law that human minds could inkling of the coming of Darwin). Apes, and approved of and admitted…” Those lege. George III took to Jay and made him King’s was the first school to graduate a ultimately, if not immediately, understand. however, are not humans, a difference that legal regulations implied that some form a knight in 1763, which gave Jay standing to medical class, Robert Tucker and Samuel Vesalius noticed and thought was signifi- of training and coursework was going to petition the governors of King’s college. Jay Kissam, which it did in 1769. Robert Tuck- Rationalism, after Thales, was quite popu- cant. When Vesalius did his own dissec- be necessary. Examination, approval, and urged the governors to make King’s Col- er went on to receive America’s first doc- lar in the ancient world and peaked in then tions, therefore, his observations naturally admission provide a fine rationale for a lege a university, which included a college of torate in medicine, from King’s College in contemporary medicine with the works of differed from those of Galen. Vesalius’ for- college, the establishment of which soon medicine “…which will add such reputation 1770. Transformative events were brewing about 400 BCE. Because the mer teachers became formidable enemies, followed. The right people were available as will give it preeminence in every respect in New York, however, which would soon fame of Hippocrates was so transcendent, which was fine in the sense that in order and Vesalius had set a precedent that trav- above every institution in America”. This end, in 1776, the initial burst of medical many authors, no doubt out of deference to to refute Vesalius, they too had to dissect eled across the Atlantic, even to what ap- was an appealing suggestion, preeminence energy at King’s College. the master signed his name to their work; and observe. It is one thing to read a book peared to European contemporaries as a being then the same desirable trait that it is therefore, whether or not Hippocrates was (by Galen or anyone else) and ask people land that was distant, somewhat strange, today. Jay thought that 5 professors would Samuel Bard, MD, one of the founders Samuel Clossy may have come from Dublin, of King’s College

6 7 History of Anatomy at Columbia from Genesis to Merger and Acquisition continued A Tradition of Teaching Gross Anatomy at The College of Physicians and Surgeons

By Paulette Bernd, PhD but he was a devoted Tory. His students faculty and teaching was not going well in the bang of the American Revolution, the It may seem a little the course for more than 40 years. Tuan clinical expertise in the form of correlation were something else. Classes became tu- any of the courses assigned to the depart- last Professor, Michael Gershon, went out strange that I was Pham, a relative newcomer to the group, lectures and laboratory demonstrations. We multuous as ties with England became ten- ment. Hours devoted to the teaching of without a whisper as the Department that asked to write this has only taught for 26 years. This dedica- are also very fortunate to have three surgeons uous. Controversial wars, like a later one anatomy, histology and neuroanatomy had started the school merged out of a free- piece on the past tion is also true of former faculty, such as teaching throughout the course, Warren fought by Americans in Vietnam, compli- drastically been curtailed, but the material standing existence. Before the merger, Cell 25 years of Gross Rick Ambron, Mel Moss, Chuck Ely and Widmann, Anette Wu and Mark Erlich. All cate the calm and concentration needed presented was not. Teachers spoke faster. Biology had become integral to Anatomy, Anatomy since I Fritz Agate. All of the Gross Anatomy of these individuals add a clinical perspective No one was happy; students blamed the which was reflected officially when depart- only joined the faculty have been lauded by medical and to Gross Anatomy that is valued by both stu- faculty in surveys and the faculty blamed ment’s name was changed from Anatomy faculty less than dental students over the decades, receiving dents and the Anatomy faculty. the students, who they thought had lost to Anatomy and Cell Biology. Cell Biology 4 years ago. However, I earned my PhD many awards. interest in learning. Research within the had also been incorporated into Pathology from Columbia’s Department of Anatomy The new Gross Anatomy course has been department was moribund and anything albeit not into the name of that depart- in 1980 and therefore have the perspec- My onerous task upon arriving back at running for three years and has been well other than description was suspect. The ment. The merger thus made sense, two tive of both student and faculty. Let me Columbia was to create a Gross Anatomy received by students. Columbia can be search committee discovered that replac- departments with cell biology as a com- begin by saying that I received a superb course for the new curriculum that neces- proud of the anatomical knowledge that ing an angry leader with a new Chair was mon activity became one, Pathology and education in Gross Anatomy here and was sitated shortening a 6-month course to our graduates carry forward with them, not easy; a succession of distinguished Cell Biology. In union, moreover, there is lucky to be mentored by many of the Gross a 4-month one. My primary goal was to both now and for the past several decades. candidates came, looked, and left. The -de strength. The merger leaves the original Anatomy teaching faculty. The course maintain the functional and clinical focus partment drifted in its discontent but by vision of Samuel Clossy intact; he searched that I took was created by Mel Moss and of the original course but to also empha- Dr. Paulette Bernd joined the Department of the time it was my turn to be interviewed, for the anatomical basis of disease and Ernie April with the intention of stressing size team-based learning both in and out Pathology and Cell Biology in 2008 after a the former Chair had died and the major thus would have been quite comfortable the functional and clinical importance of of the dissection lab, as well as modern 21-year career at the SUNY Downstate Medi- impediment to rebuilding the department had he been a member of today’s Depart- Gross Anatomy rather than minutiae. This imaging techniques, the primary way most cal Center, where she was a Distinguished was no longer present. The Chair had be- ment of Pathology and Cell Biology. The approach was revolutionary at the time clinicians see the inside of the body. The Teaching Professor of Anatomy & Cell Biol- Neuronal elements in the gut. This is of a small come an attractive one. I understood that Department’s teaching of the tradition of and transformed Gross Anatomy into a renovation of teaching space allows us to ogy. She earned a PhD under the guidance nerve in the submucosa of the bowel wall, im- whatever I did would be a success; virtu- Vesalius can “delight” students today just course that was both relevant and exciting conduct small group sessions that are in of Dr. Michael Gershon. Paulette then did a munostained to show tyrosine hydroxylase. The ally anything that changed would have to as Clossy’s lectures in that tradition used to for students. turn benefited by the recent addition of postdoctoral fellowship in the laboratory of markers = 500 nm. be for the better, worse was not possible. delight students in his time. Microscopic numerous models. Dr. Lloyd Greene at NYU. Paulette has won research within the newly merged Depart- The commitment of the Gross Anatomy several teaching awards during her career but The tenured faculty met with me upon my ment produces images that Leewenhoek faculty to Columbia has been incred- I have also been able to expand upon the is particularly proud of the “Golden Scissors” to study academic subjects, like anatomy. arrival at Columbia and assured me that would have appreciated. Columbia may ible. For example, the current faculty in- involvement of clinicians in the course as a award presented by the P&S Class of 2013, the Clossy’s lectures might once have been while they all thought I might be quite now lack a department of Anatomy but clude Ernie April and Phil Brandt, both of result of the generous cooperation of many first to take her new Gross Anatomy course. greeted with “delight”, but with the com- stellar, I was the wrong person for this job. anatomy is still alive and well at Columbia. whom were my teachers and have taught medical school faculty who provide their ing of the Redcoats, he found lectures im- Dean Tapley disagreed with this assess- possible to present and he was forced to ment and let me make changes, the most cancel classes while he raged in his diary important of which was to introduce Cell From the Doetsch Lab- about radicals (not the Red Sox) descend- Biology to Anatomy at Columbia and to the site of stem cells in the brain ing on his adopted city from Boston. In alter the composition of the faculty. New 1776, the old King’s College of medicine people, both junior and senior were re- suspended activity for the duration as Brit- cruited, research began in earnest, grants ish troops occupied New York. The school were obtained, the graduate program was re-opened in 1784, now as Columbia Col- revived and the material taught was made lege, and in December of that year, classes to correspond to the time available to in the medical school re-started. Samuel teach it. Faculty and students ceased to be Bard was named dean in 1791 but no more at odds with one another. Joint appoint- was heard, at least in the Columbia con- ments facilitated collaborations with cell text, of Samuel Clossy. biologists across departmental boundar- ies, particularly with the new and very dif- I was the last Professor of Anatomy at ferent Department of Pathology rebuilt by Columbia and had no idea that I was to Michael Shelanski. Cell biology was thriv- assume that status when I moved to Co- ing at Columbia and disciplinary bound- lumbia from Cornell. Moving across town aries were blurring. was easy, but that was the only easy part. Neuronal Stem Cells in the Brain My immediate predecessor had been fired Immunogold labeling for Aquaporin 4 reveals While the first Professor of Anatomy at the from his role as Chairman but stayed on as astrocyte endfeet around blood vessels in the school that was to become Columbia Uni- adult subventricular zone neural stem cell niche. a disgruntled professor. Curricular chang- versity P&S, Samuel Clossy, went out with Courtesy of Masoud Tavazoie and Fiona es had been imposed on an un-accepting Doetsch and Kristy Brown Lowe Library. Photo by Charles Manley 8 9 Anatomic Pathology Anatomic Pathology

Columbia “Next Gen” Columbia Anatomic Pathology Division of , the past 25 years By Govind Bhagat M.B.B.S Glen Markowitz, MD, Vice-Chairman for Operations The New Millenium Despite seminal the diverse and unique types of specimens formal ACGME accreditation was obtained By Alain Borczuk, MD work performed in that come through the Department of Pa- in July 2000 to train two fellows per year. Vice-Chairman for Anatomic Pathology I came to Columbia tained a hybrid environment that appears University Medi- to best meet the needs of the faculty and the Department of thology, faculty members of the Division of The fellowship program has grown in stature Pathology at Co- Hematopathology have made contributions to be recognized as one of the preeminent It is hard to have a cal Center as a renal residents. While the renal, neuro-, he- lumbia University in the field of neoplastic disorders of the he- training programs, attracting the finest can- 25 year perspective pathology fellow in mato-, gynecologic, and oral pathologists over the last cen- matologic system. Drs. Knowles and Chad- didates in the country. The hematopathology after only 17 years 1997 and joined the are ensconced in their subspecialties, the tury, leading to the burn developed one of the first classification faculty has contributed to over 200 presenta- in pathology with faculty as an As- majority of the department continues to characterization of systems for lymphomas arising after solid tions at national and international meetings 12 at Columbia. By sistant Professor of work as both general pathologists and sub- epithelial and mes- organ transplantation in the mid 1990s and and workshops over the past decade and its all descriptions, specialists. In my narrow “15 year view”, it enchymal tumors, with the help of Drs. Dalla-Favera and Ing- members have had a prodigious scholastic anatomic pathology in 1998. It has been is hard to imagine that Anatomic Pathol- comprehending the diversity of hematopoi- hirami characterized molecular lesions as- record, publishing over 150 peer reviewed went from separate an honor and plea- ogy at Columbia existed before the likes of etic and lymphoid had to wait sociated with lymphomas occurring in HIV manuscripts and book chapters over the units to a more uni- sure to be a part of this Department for the Drs. Perzin, Richart, O’Toole, Lefkowitch, till the 1980s when the techniques of immu- infected individuals and also described new same time period. Both Drs. Bhagat and fied division with a past 15 years. Rotterdam, Goldman, Tanji and D’Agati, to nohistochemistry were developed and mo- lymphoma entities. Alobeid have been invited to present at state, centralized laboratory in the first part of name a few. lecular biologic tools began to be used for national, and international meetings. The the last 25 years. By 1999, when I joined Although it is difficult to summarize the diagnostic purposes. The last 25 years have Members of the division assisted Drs. Chang Division has been an early adopter of new the department, much of this had already events in Columbia Anatomic Pathology Our colleagues speak of next generation seen major advances in the field of hemato- and Moore in the discovery of the Kaposi technology. Over the past decade, Southern occurred. Some of the major changes since over the past 15 years, the simple theme (“Next Gen”) DNA sequencing; my fo- pathology, many spearheaded by members sarcoma associated Herpes virus (KSHV/ Blots have given way to PCR-based assays for then have included an increase in volume has been progress. I can remember an an- cus in this entry is on the “Next Gen of of our faculty. Dr. Daniel M. Knowles was HHV8) in 1994. Since 1995, the division has diagnosing hematologic disorders and next requiring an emphasis on quality assur- tiquated gross room filled with the odor of pathology” or, more specifically, the pa- an early adopter of immunohistochemi- been led by Drs. Barbara Osborne, Anne generation sequencing is around the corner. ance. For example, the immunohisto- formalin; we now have excellent fumigation thologists who have begun their careers cal techniques to study the immune ar- Matsushima, Attilio Orazi, Bachir Alobeid, Having access to state of the art laboratories chemistry laboratory went from a mixture and an expanded, twice renovated facility. in our department during these 15 years chitecture of lymphoid tissue by applying and Govind Bhagat. Over the past 15 years, in the Department of Pathology and Cell Bi- of manual staining and semi-automation I can recall an old residents’ room with a and benefited from the modern environ- reagents developed for to the division has grown from a one member ology has allowed integration of information to a high throughput automated service. dilapidated red leather coach; we now have ment. We have recruited excellent young frozen and later formaldehyde fixed tissue operation handling 1200 cases/year to three from the immunogenetics, molecular diag- The continuous barcoding through the a wonderful facility for residents, equipped assistant professors, some of whom have specimens. In collaboration with other fac- full time faculty members and a technologist nostics, and cancer cytogenetics laboratories, laboratory has allowed for an unprecedent- to meet all of their needs. There have been risen to full professor. We have watched ulty members, he also characterized ecto- diagnosing over 4000 cases/year. Although enabling timely and accurate diagnoses and ed ability to track and organize, assuring various challenges with respect to staffing one of our residents, Dr. Bhagat, simi- pic lymphoid tissue developing in states of a fellowship program in Hematopathology opening avenues for research in the field of specimen integrity. The faculty and staff and office space, and these have been largely larly ascend. We have others who are chronic . Taking advantage of had been in existence for over two decades, hematologic neoplasia. have shown incredible resilience in the face corrected. I can recollect numerous com- on the same trajectory, and a promis- of such major changes. plaints with respect to the service, ing group of young assistant professors. and these have all been remedied under the During these 15 years, we have watched The Ob/Gyn Division and its Dedication to Women’s But the ultimate measure of anatomic pa- guidance of Doreen Hebert. We have mark- some of our “Next Gen” of residents and By Ralph Richart, MD, Former Division Director thology progress is diagnostic accuracy. edly upgraded technology and quality in young faculty depart for green pastures, The Division of Obstetrical & Gynecologi- anogenital tract (LGT). The Division was The level of science practiced by the Divi- As we strive to improve our diagnoses tissue processing, , with former colleagues holding faculty cal Pathology was established in the 1960s a world leader in the study of LGT disease sion, the skills and dedication of the fac- through continuous education and devel- and in situ hybridization. Quality assurance positions at Cornell, Mount Sinai, Me- as part of a national wave of subspecialty for 50 years and made major contributions ulty and fellows, and the support of the opment of subspecialization, new method- has emerged as a major focus for our de- morial Sloan Kettering, University of surgical pathology units in major American to the understanding of the natural history Hospital and the Department of Pathology ologies have evolved requiring incorpora- partment, and we have invested in the “next Pittsburgh, Stanford University, Univer- hospitals and medical schools. Cytology, an of LGT, its etiology, its epidemiology, and made the Division a consistently challeng- tion. Our immunohistochemistry panels gen” of QA, advanced barcode technology. sity of Michigan, and the Mayo Clinic. up-and-coming discipline, was added to the its clinical management. ing and exciting place to work. It was fun are more complex and increasingly likely The department has created a supportive Division in 1965. to come in every morning. to resolve difficult cases. We regularly -in Rather than becoming a department with environment for the “Next Gen”, and the The Division was a magnet for attracting corporate new technologies to better estab- pure subspecialty sign out, we have main- “Next Gen” has flourished. fellows and associates from the U.S. and None of these Divisional accomplishments lish our initial impressions, and it is clear abroad whose presence was a constant would have been possible without the dedi- that diagnostic uses of and whose work and publications led to cation of a smart, hard-working, involved will continue to enhance this process. All subsequent careers as division directors in support staff who were an integral part of of this added complexity and a reduction other institutions, chairpersons, and even the team. in turn around time – progress indeed! deans. The level of research was consistent- ly world class and led to the Division’s pub- The Division has now been merged with oth- lications of more than 700 peer reviewed ers. However, all the faculty, fellows, and staff articles, not to mention at least ten books, will have garnered their small place in his- Pap smear, courtesy of Dr. Anjali Saqi countless contributions to LGT courses, tory and can be proud of their contributions The Division’s major academic interests the establishment of specialized treatment in creating new knowledge and passing it on. revolved around gynecologic cancer with modality clinics, and numerous honors be- We were all privileged to play our part and to a special interest in neoplasia of the lower stowed on the faculty by their peers. make major contributions to improving the Diagnosis: malaria Ragged red fibers in a diagnosis of muscle disease. Courtesy of Kurenai Tanji, MD health care of women-our ultimate goal.

10 11 Anatomic Pathology Anatomic Pathology

A Short History of the director of the United States and Canadian electron microscopy. All EM scoping was Academy of Pathology. In 1983, as Dr. Sil- performed by the pathologist. In the days Renal Pathology Division va was about to leave Columbia to become before digital imaging systems, it could By Vivette D’Agati, MD Director of Surgical Pathology at Univer- take hours to scope a single case because sity of Texas Southwestern, I was just com- the negatives had to be developed by hand, The Renal Pathology Division of Anatomic pleting my Pathology Residency at Colum- the plates reloaded and the vacuum re- Pathology at Columbia University, which bia. I had already taken an unusual route established multiple times in a day. As the was founded in 1973 by Dr. Conrad L. Pira- by doing a year of specialization in renal size of the laboratory grew, all this was to ni, actually has its roots in Chicago. Dr. Pi- pathology as a first year resident (which I change rapidly in the years to follow. rani, a pioneer in nephropathology based at volunteered for because Dr. Pirani had no the University of Illinois, had been studying fellow that year and my group of incoming The laboratory now has 5 full-time dedi- percutaneous renal biopsies since they were residents was large). I did a second year of Visiting Italian nephrologist Dr. Belgioioso, cated renal pathologists, with the addi- introduced as a new diagnostic technique in specialization in 1983 through a National and Vivette D’Agati (renal fellow) in 1984 (in the tions of Dr. Glen Markowitz in 1998, Dr. original renal pathology laboratory BB1428). 1952. He tried to make sense of these small Kidney Foundation Research Fellowship M. Barry Stokes in 2002, Dr. Samih Nasr specimens using thin light microscopic sec- Grant to study lupus nephritis. As it turned basic scientists he was recruiting. This was in 2005 (who left to join the Mayo Clinic in tioning and the application of special stains out, I was to be Dr. Pirani’s last fellow and convenient for me because I was also sign- 2009), Dr. Leal Herlitz in 2009 and Dr. Eric (such as periodic acid Schiff, trichrome and succeeded him as Division Director upon ing out in Surgical Pathology in those early Campenot in 2011. Drs. Markowitz, Nasr Jones methenamine silver) to highlight re- his retirement in 1984. I guess you could days. In 1987, the renal pathology labora- and Herlitz received renal pathology fellow- nal basement membranes and immune de- say I was fortunate to be in the right place tory moved to a small portion of the space ship training at Columbia; Dr. Stokes did his posits. Over the next decade, the application at the right time. now occupied by the surgical pathology fellowship at University of Washington and of direct and electron secretaries, followed by a brief sojourn of was an attending at New York University Drs. Conrad Pirani and Fred Silva signing out renal biopsies circa 1976 microscopy would become invaluable tools When I became division director in 1984, nearly 2 years on the 16th floor in Ob-Gyn before joining Columbia, while Dr. Campe- in the diagnostic armamentarium of the re- the renal pathology laboratory was locat- pathology while the current laboratory in not was trained in nephropathology at the Major areas of research include pathogen- by the nephrology fellows as their most nal pathologist. ed on the 14th floor of the Black Building VC14-224 was under construction. The University of North Carolina, Chapel Hill. esis of focal segmental glomerulosclerosis, valuable teaching conference in the medical (Room 1428). Because this large room had new laboratory was completed in 1996, at In addition to a secretary, Rozanne Xavier, HIV-associated nephropathy, lupus ne- center. The tradition of the weekly clinical- At the time Dr. Pirani was recruited to been designed as a chemistry lab, much of which time I was the sole renal patholo- and 2 transcriptionists, Robin Miller and phritis and drug toxicities. NIH-funded pathologic conference was instituted by Dr. Columbia University by our former chair- the space was unusable for our purposes. gist handling a case load of approximately Ava Scanlon, the laboratory staff includes 8 research is directed to mechanisms of Pirani in the 1970’s and has followed in a man, Donald West King, he was one of the In fact our histology technician and IF 750 biopsies per year (3-fold more biop- technicians skilled in the processing of re- podocyte injury and glomerulosclerosis similar format to this day (even as Power- few renal pathologists in the country. Dr. facilities had to be housed in neighboring sies than in Dr. Pirani’s time but without nal biopsies by light, immunofluorescence in focal segmental glomerulosclerosis and point has replaced the old Kodachrome pro- King was a strong advocate of organ-spe- space (Room 14-503), which was an inef- a renal secretary!). We had only 2 very and electron microscopy. Much of the tech- HIV-associated nephropathy as well as the jectors). Drs. Markowitz, Stokes and Herlitz cific sub-specialization within anatomic ficient way to work. One of the first things energetic and dedicated technicians at nical work continues to be done by hand, identification of new biomarkers in chron- also provide continuing education to the pathology and aimed to create a center of Dr. Shelanski did upon becoming chair that time: Llewellyn (“Tony”) Ward per- with minimal automation, ensuring maxi- ic kidney disease (CKD). The Columbia many referring nephrologists throughout excellence for medical renal pathology that in 1987 was to relocate the lab to VC-14 formed light microscopy and immuno- mal quality control. Renal Pathology Division has hosted sev- the tri-state area through regional renal bi- would be distinct from urologic pathology. in order to centralize the diagnostic divi- fluorescence, while Hildegard Gutwil did eral important international consensus opsy conferences. Committed to advancing (Prior to this time, the urologic patholo- sions and provide more bench space for the the embedding and grid preparation for The laboratory now receives approximate- conferences on the classification of renal education in the field, the Columbia renal gist, Dr. Myron Tannenbaum was reading ly 3700 renal biopsies per year, including diseases, including the first working group pathologists are invited regularly to lecture the medical renal biopsies by light micros- native and allograft biopsies, of which classification of focal segmental glomeru- at annual meetings of the American Society copy only.) Dr. Pirani once confessed to me approximately 800 originate within Co- losclerosis and a revision of the WHO clas- of Nephrology (ASN), the United States and that his main impetus to leave the intel- lumbia Presbyterian Medical Center and sification of lupus nephritis. Canadian Academy of Pathology (USCAP), lectually stimulating environment he had 2900 are sent as wet tissue from over 400 and the World Congress of Nephrology, enjoyed at University of Illinois was not nephrologists at academic and communi- The Renal Pathology Division runs an an- among others. the prospect of working at Columbia, but ty-based medical centers within 12 states nual postgraduate course “Renal Biopsy in Dr. King’s promise that he would have his (spanning a broad geographic base that ex- Medical Diseases of the Kidney”, which Dr. Shelanski has guided the renal pathol- own personal secretary. In those days be- tends from Rhode Island to Florida, and as is now in its 35th year. The 4-day course, ogy laboratory into the modern age of fore the use of dictaphones or computers, far west as Indiana). Because most of our which is given jointly with the Division while preserving the a dedicated secretary was critical to a pro- material comes from outside the medical of Nephrology, provides a comprehensive legacy of specialized clinical-pathologic fessor’s clinical and academic productivity. center, we report our findings by telephone update of major diagnostic entities in ne- diagnosis using the traditional (but updat- So as chance would have it, the future of to the referring nephrologist, at which time phropathology, with emphasis on clinical ed) tools that Dr. Pirani introduced nearly the renal pathology division of Columbia we provide clinical-pathologic correla- correlations and . The longest 4 decades earlier. He has appreciated the University would turn on a personal sec- tions and discuss treatment options. This running CME course at Columbia Univer- particular demands of practicing medical, retary, who in those days was none other personal approach defines the style of our sity Medical Center, it is attended annu- as opposed to surgical, pathology and has than Eileen Erceg. practice, which is one of the largest in the ally by approximately 250 registrants from supported the laboratory’s continued spe- country. Our biopsy database provides a over 30 countries. cialization and growth to become one of Dr. Pirani trained many fellows in his ten- valuable resource for fellowship training, the largest and most influential laborato- ure at Columbia, including Fred Silva, who The legendary basketball player Alonzo Mourning received a kidney transplant and has clinical-pathologic studies and basic re- The Division hosts a weekly in-house renal ries of its type in the country. would become the executive secretary and graciously helped our department. From left: Glen Markowitz, Agnes Fogo (Vanderbilt search using archival human renal tissue. biopsy conference, which has been ranked University), Vivette D’Agati and Gerald Appel.

12 13 Surgical Pathology My (First) 56 Years at Columbia by Doctor Karl Perzin

flecting the hospital’s role as a quaternary the next day. Big resections, on the other Dr. Karl Perzin’s History of the Department is an extensive work in progress. Here we present the first few paragraphs. Details of the years A Transformative care referral center. At the opposite end hand, were often left fixing in the gross that followed these will appear on the Pathology and Cell Biology Website for which we are planning a new History Section and then a Quarter Century for of the spectrum, we are seeing increasing room for days until the resident found time publication. Dr. Perzin’s many years of teaching have been recognized by the Perzin Teaching Award, given to Attendings for their efforts numbers of fine needle biopsies not much to submit sections, and no one got too up- in teaching Residents. Surgical Pathology thicker than thread. These biopsies usually set. Now, all specimens are on a fairly rigid By Kathleen O’Toole, MD represent an attempt to diagnose a deeply timetable whereby all but a small subset of My first encounter with the Division of When the Columbia Presbyterian Medical situated tumor using a minimally invasive diagnostically difficult cases are completed Surgical Pathology was in the spring of Center was established in 1928, each Hos- When I began reflecting on the last 25 approach. The irony is that these tiny spec- within three working days of their arrival the second year (1956), in a course called pital or Division had its own pathologist. years, I was dumbfounded by all the imens often require an extensive panel of in the division. “Introduction to Surgery”, in which we The Medical School had a Pathology De- changes that had occurred. For those of us immunohistochemical stains for accurate were taught about granulation tissue and partment. These pathologists did , who were around back then, the changes diagnosis, and it’s not uncommon that we Finally, the financial aspects of the division the principles of . At that taught the second year pathology course, were gradual. However, the cumulative run out of material. have undergone a sea change since 1987. time, the Division of Surgical Pathology conducted research, and participated in changes have been so profound that the Back then, we were completely dependent was part of the Department of Surgery and various conferences, such as the CPC (the Division of Surgical Pathology has under- Other changes have come about largely be- on the hospital for all revenue, a fact that my instructor in the lab was Dr. Virginia clinico-pathologic conference, which was a gone a complete transformation in a rela- cause of the ever increasing role played by was reflected in our salaries. We had a Kneeland Frantz, a Professor of Surgery. major weekly event for many years). The Pa- tively short time. various regulatory bodies. Back in 1987, the primitive system whereby specimens were thologist at Babies Hospital was Dr. Doro- only manuals we had included binders con- classified into four categories: small or large, At P&S, the third year was a full 12 month thy Anderson, who, I was told, first showed By far the most obvious change is in the taining recipes for the stains used in histol- and inpatient or outpatient. The triplicate year, without vacations. (Three months that Celiac Disease and Cystic Fibrosis were number of specimens processed. In 1987, ogy, instruction manuals that accompanied copy of the requisition slip was stamped Medicine, three months Surgery, divided different entities. The Pathologist at the there were 15,488 cases accessioned in our equipment, and crude diagrams in the with the appropriate category, and those between General Surgery and Surgical Neurologic Institute was Dr. Abner Wolff; Surgical Pathology; in 2011, that number gross room illustrating how tissue sections were sent to the hospital to be processed for Subspecialties, three months divided be- at the New York Orthopedic Hospital was totaled 33,647. This dramatic increase re- were to be labeled. In preparation for our eventual payment to the Pathology depart- tween Neurology and Psychiatry, and three Dr. Zent Garber, at the Squire Urologic flects not only the absorption into Surgi- first CAP inspection in 1995, we had to cre- ment. Beginning around 1990 with the cre- In this essay, I describe some of the major months divided between Pediatrics and Ob- Clinic was Dr. Meyer Melicow, at the Sloan cal Pathology of all cardiac and pediatric ate highly detailed procedure manuals for ation of an incorporated practice plan, the events that occurred during the years 1955- Gyn). During the six week General Surgery Hospital for Women was Dr. Engler, and surgical specimens, but also the striking each of the functional units in the division. revenue began increasing. 1987, before Dr. Shelanski became chair- rotation, students came to the Surgical Pa- at the Eye Institute was Dr. Reese. Surgical increase in the number of hospital proce- Those manuals must be constantly updated man. In speaking with various current thology Laboratory twice a week. There was specimens removed by Surgeons in Gen- dures. Whether performed in operating by our lab supervisors as they are the prima- These are just a few of the many changes members of our Department, I have found a classroom where the Pathology Residents eral Surgery (and ENT) were studied by the rooms or in endoscopy, cystoscopy, mam- ry focus of any lab inspection. Also because that have taken place, but they’re the ones I that most are unaware of these events. I will Room is now, with the blackboard wall fac- Pathologists in the Division of Surgical Pa- mography, cardiac catheterization or in- of increased regulations and government consider most significant. For me and prob- concentrate on the structure of Pathology ing the Humphreys Auditorium, and with thology, which was part of the Department terventional radiology suites, procedures mandates, our reports have become highly ably for others of my vintage, the Surgical services, especially on the major reorgani- five rows of benches containing cabinets in of Surgery. In the late 1950’s, when I was a generally generate tissue specimens. standardized. Particularly for cancer cases, Pathology of today is a totally different en- zation that occurred in 1960. I will also de- which we locked our . Each of medical student, the Surgical Pathologists there are numerous items that must be in- tity as compared to what it was 25 years ago. scribe the changes that have occurred in the us was given a box of glass study slides. I were Dr. Frantz, Dr. Lattes, and Dr. Lane. It’s even more complicated because the cluded for a report to be considered an ac- People who have only recently joined us teaching of Surgical Pathology to our medi- remember being given a metal tray contain- Dr. Arthur Purdy Stout had retired in about number of cases accessioned doesn’t con- ceptable one. The quality of our reports is a have no idea how far we’ve come. This posi- cal students. I also reminisce about sev- ing a formalin fixed gall bladder to exam- 1950, at the mandatory retirement age of 65, vey the actual number of specimens we are key factor in determining the hospital’s eli- tive trajectory will surely continue. eral individuals I knew during this period, ine. My instructor in the lab again was Dr. but he continued to act as consulting Pa- dealing with. Back then, a prostate biopsy gibility for various accreditations including including Drs. Virginia Kneeland Frantz, Virginia Kneeland Frantz. thologist until 1968, when he died at age 83. consisted of one or at most two containers. that of the JCAHO. Kathleen O’Toole began her residency in Arthur Purdy Stout, Raffaele Lattes, Nathan Today, the typical prostate biopsy includes Anatomic Pathology at Columbia in 1978. Lane, and Donald West King. In the third year, in addition to the Laboratory, I graduated from P&S in June 1958, and twelve containers, each containing one or Regulatory activity has also impacted our Except for a 10 month fling with commu- there was a Surgical Pathology lecture course, returned in July, 1961. While I was gone, more cores from a uniquely designated turnaround time. In the old days, biopsies nity hospital pathology in 1989, she’s been I first came to the Medical Center in Sep- which was given every Saturday morn- Dr. H. P. Smith had retired as Chairman site. This counts as one case, but in real- were generally reviewed and signed out here ever since. tember, 1954 as a first year medical stu- ing, starting in September and lasting until of the Pathology Department. Dr. Donald ity, there are twelve different biopsies, each dent. My first encounter with the Pathol- March. The setting was the Humphrey’s Au- McKay was recruited from Boston to be of which must be evaluated and reported ogy Department was in September, 1955. ditorium, which was twice the size it is now, the new Chairman, but he only came with on. Similarly, back then breast cancer was On the first laboratory day, the Chairman room enough for the entire class. The first part the proviso that all the various Pathology treated with mastectomy or sometimes of the Pathology Department, Dr. H. P. of each lecture consisted of a discussion of an Laboratories be unified into the Pathology lumpectomy. Now, we will frequently re- Smith, told us that we had to buy color- entity by a surgeon, followed by a presentation Department. The merger of the various ceive a lumpectomy accompanied by one ing pencils, smudge sticks, and an unlined of the pathologic findings by a Surgical Pa- laboratories resulted in a unified Pathol- or several sentinel node biopsies and six notebook, into which we were to make, in thologist. One example was Crohn’s Disease ogy Training program. As far as I can re- additional margin resections. Again, one each lab session, a drawing of something with the surgeon Dr. Frank Gump, discussing member, Dermatopathology and Eye Pa- case, but infinitely more complicated, re- we examined from one of our slides. The its clinical aspect, and Dr. Raffaele Lattes de- thology remained separate entities. These quiring additional labor in the gross room drawings were part of our final grade. scribing the pathologic features. The Surgical changes were crucial to the Department and histology lab, not to mention the pa- Many students were offended (imagine – Pathology discussors were Drs. Frantz, Lattes, we know today. thologists’ time spent signing out. a coloring book in medical school!) but, Lane, and Ozzello. This course was ended in in retrospect, those exercises helped us to the late 1960’s. During the student rebellion While we do see some simple, straightfor- critically examine what we were supposed years of that time, almost all Saturday teach- The remainder of Dr. Perzin’s recollections ward cases, we have a very high percentage to be seeing through the . ing functions were terminated. will appear on the Website and in other forms. of large and extremely complex cases re- The view looking south from the medical center. Photo by Richard Miller 14 15 Laboratory Medicine (Clinical Pathology) The Institute for Cancer Genetics

A Treatment By Richard Baer, PhD for Rh disease The Institute for Cancer Genetics (ICG) (1999-2005), before moving to the Irving By Eldad Hod, MD was established in 1999 from a nucleus of Cancer Research Building in 2005. With cancer researchers in the Department of the recruitment of key investigators (Anto- Rh disease, a form of hemolytic disease of nosuppressive” therapy currently approved Pathology. The goal of the ICG was to elu- nio Iavarone, Anna Lasorella, Adolfo Fer- the fetus and newborn, used to claim the for use in humans. Investigation into the cidate the biological processes that cause rando, Jean Gautier, Jose Silva, Shan Zha, lives of approximately 10,000 babies annu- mechanisms underlying immunization to human cancer, and translate these discov- and Bin Zheng), the scope of ICG research ally in the United States alone. However, red blood cell antigens and immune-me- eries into new strategies for improved pre- now encompasses many of the critical ar- it was virtually eradicated in the 1960’s diated hemolytic reactions continues in the vention, diagnosis, and therapy. To achieve eas of human oncology and represents the thanks to the efforts of Drs. Vincent Freda Department of Pathology & Cell Biology at these aims, Dr. Riccardo Dalla-Favera, the largest concentration of cancer-related sci- and John Gorman at Columbia Presbyte- Columbia University Medical Center; the founding ICG Director, assembled a strong ence at Columbia University. One simple rian Hospital. Dr. Freda, an obstetrician, additional insights gained may allow this group of investigators who would pursue measure of this expansion is the level of and Dr. Gorman, who completed his resi- type of immunomodulatory therapy to be independent cancer-related research pro- funding from peer-reviewed grants for re- dency training in Anatomic and Clinical used in other clinical settings. grams while exploiting a shared organi- search and training, which has increased Pathology at Columbia in 1960 and who zational and cultural framework. With from ~$1.5 million in 1999 to over $10.0 was the Director at Columbia, the early support and encouragement of million in 2012 (annual direct costs). As were awarded the Albert Lasker Award for Dr. Shelanski, the initial ICG laboratories most of its current faculty still enjoy pri- Clinical Medical Research in 1980 for their Eldad Hod and Steven Spitalnik studiy the stability were comprised entirely of faculty from the mary appointments in the Department of role in virtually eliminating this devastat- of red blood cells. Dr. Spitalnik is Vice Chair and Typing Lung Cancers Department of Pathology, including Drs. Pathology & Cell Biology, the ICG main- ing disease. the Director of the Clinical Pathology Division. Benjamin Tycko, Ramon Parsons, Wei Gu, tains close ties to its origins after thirteen Pre-invasive Invasive and Richard Baer. The ICG originally oc- years of growth. will never work,” Drs. Freda and Gorman BAC AdCA Rh disease results from a blood group in- persisted in their research. In a landmark cupied space in the Russ-Berrie Pavilion compatibility between the mother and study published in Science in 1966, they paternally-inherited antigens on fetal red showed that passive immunization of preg- Those were the days my friend. Riccardo Dalla- blood cells. Although it can be caused by nant women, by injection of exogenous an- Favera studies a sequencing gel, back in the day. antigens other than the Rh(D) antigen, this tibodies to Rh(D) (i.e., Rh-immune globu- was the most common cause at the time; lin), within 72 hours of delivery successfully Neuronal Cells in Tissue this would still be true today had it not been prevented active maternal immunization to for Freda and Gorman’s invention of Rh- Rh(D). This led to the current standard of immune globulin treatment. Historically, practice of providing pregnant Rh-negative an Rh-negative mother (i.e., the mother women with Rh-immune globulin injec- does not express the Rh(D)-antigen on her tions twice during pregnancy and also at red blood cells) becomes immunized to the delivery. This treatment effectively prevents Rh(D)-antigen during pregnancy when women from making anti-Rh(D) antibodies to AdCA BAC relative Rh(D)-positive fetal red blood cells cross the in virtually every case, thereby preventing placenta into the maternal circulation. Dur- Rh disease. The most fascinating aspect of ing subsequent pregnancies, maternal IgG the story scientifically is that we still do not anti-Rh(D) antibodies can cross the placen- have a complete, mechanistic understand- ta into the fetal circulation and destroy the ing of how this therapy works. The original red blood cells of an Rh(D)-positive fetus. hypothesis that Rh-immune globulin func- This red blood cell destruction (i.e., hemo- tions by clearing fetal Rh(D)-positive red lysis) can produce hydrops fetalis (i.e., heart blood cells from the maternal circulation, failure due to the severe hemolytic anemia). thereby hiding this foreign antigen from the In addition, hemolysis leads to production maternal immune system, is inconsistent of bilirubin in the fetus as a by-product of with the fact that passive immunization to BAC AdCA relative hemoglobin degradation. After delivery, with Rh-immune globulin guides the fetal Microarray technology reveals genes that are bilirubin is no longer cleared by the placenta red blood cells directly to antigen present- and can accumulate in the newborn, which up-regulated (in red) and down regulated (in ing cells, the same cells responsible for ini- green) for pre-invasive bronchioloalveolar - can cause permanent brain damage (i.e., tiating an immune response to foreign anti- cinoma (on the left) and invasive mixed subtype kernicterus). gens. Thus, the story is much more complex adenocarcinoma (on the right). Each column is than initially thought. In addition, perhaps an individual tumor. Squares across represent individual genes expressed in one tumor type Although NIH Study Sections failed to fund because of this lack of mechanistic under- the project on two separate occasions, com- relative to the other. standing, the use of Rh-immune globulin Triple labeling of differentiated neuronal CAD cells. A differentiated neuronal CAD cell that was transfected with neurofilament L is shown in red. menting that their idea was “nonsense and remains the only antigen-specific “immu- Courtesy of Alain Borczuk, MD The endogenous expression of the neuronal intermediate filament alpha-internexin is labelled in green. Nuclei are labelled in blue. Courtesy of Dr. Ron Liem

16 17 The Residency Training Program The Residency Training Program

By Charles Marboe, MD Patricia Raciti, MD The Department of Graduating residents are now in positions Renwick, Shaknovich, Shevchuk). At Mt. Sneaking Up on Pathology And Representing Pathology has a long spanning the country, from Brigham & Sinai we have Dr. Singh, vice chair for CP The hallmark of the department is unques- the Younger Faculty history of training Womens Hospital in Boston, to the Hos- and Dr. Thaker, vice chair for AP, as well as tionably teamwork. As a junior resident, I Andy Teich, MD, PhD men and women pital of the University of , the Dr. Foitl and Dr. Pessin-Minsley. At NYU have seen this characteristic displayed most for careers in the University of Pittsburgh, East Carolina we have Drs. Barisoni, Littman, O’Neill, evidently in the time and care senior resi- clinical practice of University, the University of Florida, the Simsir, Singh. Our beloved colleague Dr. dents take to help newcomers navigate the pathology and labo- University of Miami, the USAF in Biloxi, Yee past away last year. Our graduates are environment. And, after a year here, I can ratory medicine and Mississippi, M.D. Anderson Cancer in also at Memorial Sloan Kettering Cancer see a culture of teamwork that pervades all for leadership roles Houston, the Mayo Clinic in Rochester, Center, Downstate Medical Center, Albert levels in both Anatomic and Clinical Pa- in diagnostic, aca- Cleveland Clinic, University of Wiscon- Einstein, Winthrop-University Hospital, thology. There is a mutual understanding demic, and research pathology. The train- sin, University of Michigan, UCLA, Ce- Long Island Jewish Medical Center, and St. that problems are best solved as a team and ing programs have flourished with the sup- dars Sinai, and UCSF in California, Fred Luke’s-Roosevelt. that ego must be subordinated in order to port and guidance of Mike Shelanski in his Hutchinson in Seattle, University of Colo- deliver the best patient care. tenure as Chair. The ACGME- accredited rado, and the University of Utah, among Among graduates of the program since program has 21 positions in Anatomic and others. Many graduates are in the greater 2004, 66% are in academic faculty positions. The goal of Pathology is often to give an Clinical Pathology as well as ACGME-ac- New York area including New Jersey. accurate, definitive diagnosis, yet at Co- credited fellowship programs in Hematopa- For graduates of 2004 through 2011, the lumbia there is a tremendous amount of thology, Molecular Genetic Pathology, and The department has also heartily popu- department has the gratifying, and we discussion, thought and analysis dedicated In terms of my perspective as a junior pa- Neurpathology as well as Assistant Attend- lated other departments of pathology in believe unique, experience of 100% first to seemingly straightforward cases. It is thologist, I think that one of the strongest ing Pathologist “Fellowships” in Surgical , including Cornell (Drs. time pass on the certifying examinations through this curiosity, open-mindedness themes in my training and early career has Pathology and GI/liver pathology. Knowles (chairman), Cesarman, Pirog, in anatomic pathology, clinical pathology, and commitment to correct diagnosis in been the rapid pace of change in the field. neuropathology, and hematopathology of every case that observations are noted, Not just scientifically, although there cer- the American Board of Pathology. patterns are noticed and critical discov- tainly is that, but also in terms of the shift- eries are made. As a first year resident, I ing landscape of health care, the future role Pathologists of the 1930’s have sought to categorize cases, clinging of the government in health care, and how In spite of being raised by a pathologist to what I know. Over and over, I have our relationship with other physicians will mother and surgeon father, I lacked a fo- been challenged to accept cases that sit un- change as a result of all of this. The pace cused curiosity for science and biology. In- comfortably in a “gray zone” and to view of change is so rapid that I don’t even have stead my interests wandered, first to history these cases as opportunities to advance my any conclusions, other than to simply note and literature and then finance and consult- knowledge and knowledge in the field. that things are changing. On the scientific ing, before they were finally piqued by med- side, the rise of molecular diagnostic test- icine. It was only after I opened the pages of Pathologists are by their nature imagina- ing is changing everything, especially in Robbins and Cotran’s Pathologic Basis of tive. Where others see a flat pink and blue tumor diagnosis. In my own field, every Disease that I became mesmerized by Pa- image, we see a range of colors from gray to few months another mutation is found thology. Suddenly I needed to learn more purple and sometimes, three-dimension- in a neurologic that has some about one half of my “family business.” ality. This imagination serves us well – it predictive or therapeutic significance, helps us imagine our patient standing be- and the pace of this discovery is increas- Having taken the last several years to un- fore us when only their cells are present. At ing. I’ve heard from older attendings that derstand pathology in more detail, I retro- Columbia, I have found this imagination, there used to be fellowships in “immuno- actively appreciated three “keys to success” resulting in patient care, underlies the care histochemistry” when this technique was Young Pathologists of today my mother displayed: she approaches her given to every aspect of work in the depart- first available. Of course, now everyone in- interactions with other pathologists and ment, whether grossing an organ, viewing a corporates IHC into their daily routine. I clinicians with humility; she has genu- slide, performing an autopsy or signing out suspect the same will be true of molecular ine curiosity about every case that comes a molecular test. diagnostics in a decade. On the health care across her scope; and finally, she is con- side, it’s clear that our country can’t afford stantly aware that there is a patient behind As the Department celebrates its achieve- the current health care system as it stands. every slide and test tube. ments over the last 25 years and its basic How will this be resolved? Where will pa- science discoveries continue to drive our thology fit into the new order (whatever As my first year of combined AP-CP resi- understanding of medicine, I am proud to that will be)? I have no idea. All of these dency draws to a close at Columbia-Presby- be part of a Department that emphasizes a themes together give me the sense of great terian, one aspect of the Pathology Depart- collective, collaborative approach in diag- potential as well as great uncertainty for ment I have witnessed and appreciate is the nosing and treating difficult diseases while our field. I suspect that this is always the case in a field when great things are hap- The new One World Trade Center, now visible parallel between the culture of our depart- maintaining what is fundamentally a pa- from the Medical Center ment and my mother’s “keys to success.” tient-centered attitude. pening. It’s exciting; that’s for sure.

18 Today is Better! 19 Cell Biology: Professors and Students Cell Biology: Professors and Students

Pathology News from the second brain: Mike Ger- Reinventing the The Forbidden Fruit –Cell Biology in the Department and Cell Biology shon’s laboratory identified stem cells of PhD Program a rigorous curriculum that includes basic of Pathology (1987-2005) By Lloyd Greene, PhD Liza Pon, PhD neural crest origin that give rise to enteric By Ron Liem, PhD science courses in biochemistry, cell and neurons in the bowel (see the figure in his It seems that for Riccardo Dalla-Favera, Ramon Parsons, Jan molecular biology and molecular genet- most of my career Kitajewski, Srikumar Chellapan, Antonio Ia- Mike Shelanski is well known for his inter- article). They also identified dopaminergic When the new Chair and his team arrived ics, as well as a one year course in Mecha- I’ve had Cell Biolo- varone and Richard Baer. Other bona fides est in molecular mechanisms of neurode- neurons in the enteric nervous system, and at the Department of Pathology in 1987, nisms of Human Disease and a course in gy envy. Cell Biol- like Chloe Bulinski and Gregg Gundersen generative diseases. However, many in the that enteric neurons produce oxytocin, the Graduate Program had lost accredita- . All students receive seri- ogists always seem reached out to join us. In good time, Rich- Department may not know that Mike was which acts to oppose stress. tion. There was only one NIH grant in the ous training in the Responsible Conduct to be the cool- ard Vallee came aboard and lent a mighty the first to purify “a subunit from micro- whole department. Part of the problem of Research. A number of our students est folks around. Cell Biological hand along with recruits Gil tubules” (tubulin) which has colchicine- Molecular mechanisms of disease and drug was that the students in the program were participate in the Med into Grad Program, Maybe this comes Di Paolo and Yingui Mao. So did generations binding activity. He is also one of the first discovery: Ron Liem’s laboratory found that typically not working in laboratories in a Howard Hughes Medical Institute sup- from studying the of our offspring including Carol Troy, Ben to identify a role for tubulin and microtu- pathogenic mutations in a neurofilament the Department, had not partaken in any ported program that gives graduate stu- fundamental unit of life. Words like Golgi, Tycko, Wei Gu, Darrell Yamashiro, and Pe- bules in neuronal transport, and the first to gene lead to protein aggregation in cell cul- organized curriculum, did not receive sti- dents clinical experience. The directors centrosome and endoplasmic reticulum ef- ter Canoll. Many more came, left their Cell detect cross-bridges between microtubules ture models. They have used these muta- pends, and often even paid tuition, which of the program are Drs. Ron Liem, Steve fortlessly roll off their tongues. They under- Biological imprints and then moved on in- and mitochondria in axons. In light of tions to develop a mouse model for Charcot in excellent PhD programs, is paid by the Spitalnik, Howard Worman and Patrice stand the optics on their fancy microscopes cluding John Krolewski, Tim McGraw, Paul this, it is not surprising that Cell Biology is Marie Tooth Syndrome, the most common program. To remedy these defects, we Spitalnik. The perspective of one of our for which the prices go up as the photon Fisher, Takaaki Sato, Wilma Friedman, Brett well-represented in the Department. I am inherited neurological disorder. proposed a curriculum of courses in basic students, Mike Badgley, appears elsewhere numbers go down. Ok, I’m a neurobiologist, Lauring, Gene Marcantonio, Yuan Chang, happy to report that Cell Biology continues cell and molecular biology as well as the in The Newsletter. but hey, neurons are cells too! Undergradu- and Patrick Moore. And there was always to flourish, and to describe some recent ad- Howard Worman’s lab has elucidated mechanisms of human disease, student ate Chem major, graduate degree in Chem- Chairman Quintessential himself. As a re- vances in Cell Biology in the Department. pathogenic mechanisms of diseases caused seminars, laboratory rotations and guar- Over the years, our faculty members by mutations in nuclear envelope genes istry, post-doc in the Heart Lung and Blood sult, my long-sought Cell Biological identity anteed support for the students. We were have participated heavily in several other Institute (not as bad as it sounds, but not a not only failed to sink in that dreaded mire of New mechanisms for intracellular move- and are developing novel drug treatments provisionally approved for accreditation, graduate programs at the Columbia Uni- “Cell Biology” lab either), first job in a De- pathology, but was buoyed up and flung onto ment: Richard Vallee’s lab has worked out for cardiomyopathy caused by mutations and admitted our first class in 1988. Since versity Medical Center. In addition to the partment of Neuropathology. Met a quintes- the fertile ground prepared by this host of co- the mechanism for the century-old mystery in the lamin A/C gene. that time we have developed into a vibrant Med into Grad Program, both the Inte- sential Cell Biologist along the way who po- Departmentists (no unkind thoughts please of interkinetic nuclear migration in radial and rigorous graduate program. grated Program in Cellular, Molecular lymerized and depolymerized microtubules about the nature of fertilizer – we’re talking progenitor cells in the developing brain. They Gil Di Paolo’s lab identified lipid enzyme and Biomedical Studies and the MD-PhD at will – and what did he offer? A job in a here about intellectual sustenance). Perhaps have also worked out the complete mecha- Phospholipase D2 as a key factor in Al- Among the graduates from our program programs are run by Drs. Liem and Shel- Department of Pharmacology. Finally the there were equal, but there were certainly no nism explaining how adenovirus recruits zheimer’s disease-linked synaptic dys- are Wei Gu, Professor of Pathology and anski. Both programs have long-standing quintessential Cell Biologist decided to take better places on this planet to dissect the Bi- cytoplasmic dynein to travel to the nucleus. function and cognitive deficits. They also Cell Biology at Columbia and Geri Kre- training grants that have just been re- found that the signaling lipid PI(4,5)P2 is a on a new Chair across town and again of- ology of Cells, those basic units of living mat- itzer Associate Professor of Cell Biology at newed. The Cell Biology Program is now fered a job. Horror of horrors, it was in a De- ter. We hadn’t the name, but that mountain, Gregg Gundersen’s lab discovered TAN target for Aβ oligomers, and that trisomy Cornell. Dr. Stefan Pukazki is an Assistant a subdivision of the Integrated Program, partment of Pathology. The hallways were par la force des choses, would eventually come lines (for transmembrane actin-dependent at synaptojamin 1 gene is a key contributor Profressor of Biology at the University of which is directed by myself with the criti- stacked with those bottles of pickled mal- to us. To the whirring of saws and clanking nuclear lines), the first structure to be to brain dysfunction in Down Syndrome. Alberta and works on cholera . cal assistance of Zaia Sivo, who also ad- formed innards that populate nightmares. of microtomes, Chairman Q had forged an identified in the nuclear envelope since the Chung-Liang Chien is Professor of Anat- ministers the Pathobiology Program. The I looked out the window from my new of- Eden of Cell Biology. And not entirely in his identification of nuclear pores. TAN lines Rick Ambron’s laboratory has identified omy and Associate Dean of Student Af- Vision Training Grant and the Cancer fice the first week and noticed some guys in own image! may transmit force into the nucleus and a signaling mechanism that transmits in- fairs and International Affairs, National Training Grant are directed by Drs. Carol white coats across the way in the P&S build- drives actin-dependent nuclear movement, formation from sites of nerve injury and Taiwan University. Several of our students Mason and Richard Baer, respectively. ing hunched over something that fortunately which leads to centrosome alignment and inflammation to nociceptive neuronal cell have won the Weintraub Graduate Student Dr. Mason is also one of the co-directors did not and could not rise to view. Were my polarization of migrating cells. bodies, which in turn leads to long term Award at the national level and the Dean’s of the Neurobiology and Behavior gradu- hyperexcitability, an event that is associated Cell Biological aspirations about to be sliced Award at the university level. ate program. Faculty in our department up, embedded and warehoused? Ron Liem Checkpoint control during cell division: with chronic pain. They have also devel- have students from many different gradu- and Carol Mason also made the ride across All previously characterized checkpoints oped drugs that target this pathway, which The Graduate Programs at Columbia ate programs in the Basic Medical Sci- town. Somehow they got joint appointments monitor inheritance of the nucleus and may ultimately be used to treat chronic pain University Medical Center are now con- ences, in addition to students from the in the bone fide Department of Anatomy nuclear DNA. The Pon lab has identified without sedation, tolerance or addiction. solidated under the Coordinated Doc- Pathobiology and Molecular Medicine and Cell Biology. And they didn’t even have two novel checkpoints that block cell cycle toral Programs in Biomedical Sciences. Program, the Integrated Program, the the where-with-all to be smug about it. It’s in response to defects in the inheritance of With the recruitment of new investigators Our graduate program is now called the Neurobiology and Behavior Program and said that when you’re drowning you’ll grab mitochondria and mitochondrial DNA. including Julie Canman, who admits that Program in Pathobiology and Molecular the MD-PhD Program, and the Pharma- she is obsessed with cell division and build- at anything to stay afloat. Janus-faced Ron Medicine and is part of the Graduate Pro- cology, Nutrition and Genetics programs. and Carol were a good start. Then there Yinghui Mao’s lab found that the formin ing new microscopes, Ulrich Hengst, who grams in Molecular Basis of Health and were fellow Pharmacologist-Pathologists- mDia3 can regulate microtubules, inde- studies intra-axonal mRNA translation, Disease. There are currently 25 students in Our students are the reason we come to really Cell Biologists Fred Maxfield, Ekkhart pendently of its effect on actin. They also signaling pathways that control growth the Pathobiology and Molecular Medicine work in the morning and, although manag- Trenkner and Mary Beth Hatten. Flailing identified links between the state of micro- cones, neurodegenerative disorders and Program (average five per class), includ- ing a student’s training is often not simple, about a bit more in the Department one tubule attachment to mitotic checkpoint neuronal repair, and Clarissa Waites, who ing MD-PhD students. The number and it is one of the most fulfilling experiences we struck neuropathologist cum Cell Biologist signaling at the kinetochore and accurate studies the role of ubiquitination in synap- Super-resolution structured illumination image the quality of applicants have steadily in- can have. Jim Goldman and and then an expanding chromosome segregation. tic function, it is clear that Cell Biology will creased over the years. The students have of mitochondria (red) and ER (green) in the continue to thrive. throng of Cancer (nee Cell) Biologists like budding yeast. See previous article by Lisa Pon.

20 21 Professors and Students The MD-PhD Program at 37

A Graduate Student’s group discussions have created a close-knit ed profession. Some can find comfort in the this publication shows, this dedication has By Patrice Spitalnik, MD community from which we develop sup- and the systematic unpack- developed over many decades and I am hap- Perspective port networks among fellow students and ing of research questions. And then there are py to be a part of it. The MD-PhD program accepts some of the Angela Yuanyuan Jia faculty – when experiments fail, as inevi- those of us who value not only the elegance of most exceptional students in the country. Why do we make tably they do, it is comforting to know that scientific study, but also its profound utility; Recently, Columbia has begun to support the The goal is to produce the next generation the commitment to there are half a dozen professors interested especially as applied to the management and direct interaction of student researchers and of leaders in medical research with an em- a life in science? As and eager to assist. treatment of human disease. its clinical community in an institutional phasis on the qualities of both medical and any graduate student way. In 2004, the Howard Hughes Medical scientific training. This training will enable will tell you, there is a In our department, we are united in the goal Institute (HHMI) established a grant-based our graduates to be innovative at the bench huge cost in terms of of elucidating molecular mechanisms of initiative whose primary goal would be to and to play a vital role in the translation of labor and persever- disease, for the sake of knowledge and ulti- bridge the so-called bench-bedside gap, and scientific findings to clinical research. The ance. So why do we mately to improve medical care. I am com- create a new generation of basic research- most important ingredients, therefore, are do it? Certainly not mitted to build on the scientific strengths ers who would be not only familiar with the student and the interactions of the stu- for the money or lifestyle! that I have acquired over the last few years. the terminology and processes of the clinic, dent with his or her mentors, both in medi- Wherever I go and whatever I do, the expe- but would also develop an understanding cal and in graduate training. For me, a big part of the answer is this: If riences from the Department of Pathology of important scientific questions in modern we think creatively, if we plan efficiently, will be part of me, and I am grateful. medicine. This initiative would come to be This is easily said and not so easily done. and if we execute skillfully at the lab bench known as the Med-into-Grad program. Co- At Columbia we have been able to attract ... there will be a few rare moments when Angela Jia is a fifth year graduate student. She lumbia was among the 2010 grant awardees. highly able students and our large faculty Michael Badgley (right) and his PhD advisor is involved in a broad range of research and we learn something new and surprising studies the role of microRNAs in the develop- Ken Olive study pancreatic cancer. In a mere two years, Columbia has estab- that nobody else in the world knows. This ment of bladder cancer, and additionally serves lished a new, clinically focused curriculum clinical care. MSTP training opportunities are exceptionally broad and include not is the payoff. There is so much more that as the President of the Graduate Student Advi- While most researchers likely derive moti- for 1st year Pathology students as well as co- only the traditional biomedical sciences, One of the worries about four years of re- we need to do and to learn; that’s what sory Council for the entire University. vations from an amalgamation of these mo- ordinated the pairings of a growing number but also Chemistry, Bioengineering, Bio- search is that medical skills learned in the draws me to lab every day. tivations, I have found that the final descrip- of Med-into-Grad participants and clini- medical Informatics and Epidemiology. first two years of medical school will be tion is aptly suited to myself and to the other cians to mentor them. The program contin- We encourage interdisciplinary work-one lost. We avoid this by a clinical competence I want to thank my advisor, Dr. Cordon- The Med-into-Grad students of the Pathology department. It is ues to mature as students maintain contact of our students undertook a productive training during the research years, in which Cardo, for providing me with a challeng- rare that a program’s mission, faculty, and with their clinical mentors and spend time Program: A Grad Student collaboration in bacterial evolution with students learn clinical medicine and see pa- ing and exciting research problem, and the students complement one another so well in interacting with patients. experts at the Museum of Natural History. tients one day a month. Department of Pathology for welcoming Tackles Pancreatic Cancer the pursuit of a singular goal: the improved me into an outstanding research envi- By Michael Badgley From a more personal perspective, I will say treatment of human disease through the un- Although the Medical Science Training ronment. There are a few aspects of the that this nascent program was one of the We seek a unique student. Our ideal student derstanding of basic biology. Even rarer still Program that funds the program has been Department of Pathology that I want to The desire to carry out scientific research major draws for me during my application will have had an in depth, often multi-year is the graduate program that seeks to but- in existence for 37 years, our Department’s highlight as especially important to me. springs from a variety of sources. Some aim to Columbia. Establishing a working knowl- research experience as an undergraduate tress this objective through the facilitated role dates from 1998, when, with the help Of particular significance is the commit- to satisfy curiosity regarding the “hows” and edge of basic clinical principles as taught by during which he or she would develop a interactions of working clinicians, transla- of Dr. Ron Liem and Dr. Ira Tabas, we be- ment to translational research, and by “whys” of the natural world. Others may en- an expert staff of doctors, research faculty, passion for research and a good idea of the tional researchers, and basic scientists. As came responsible for its administration. that I mean the use of knowledge from joy the prestige and trust offered by a respect- and my clinical mentor has provided me direction in which the work might lead. Ob- When we became its administrators, there model systems and model organisms to with a depth of knowledge that will grow jective evidence might include publication were 70 students in all years and now there understand the pathogenesis in human and inform my future research. Interact- and participation in scientific meetings as are 105. We could not support this number disease. Across the department, we have ing with like-minded students and finding well as knowledge of the work that extends of students without the generous support many examples of this approach, and in a laboratory whose work aims to translate beyond experimental details and methods. of the Medical School and Dean Goldman. my personal experience, I have been able directly into clinical use motivates my re- In the past 15 years, the time to completion to build on the expertise from Dr. Dalla- search. And finally, it bears special noting The MD-PhD curriculum includes 18 has been shortened. Favera’s lab, whose members have helped that in the grind of daily lab experiments, re- months devoted to the basic science cours- with miRNA analysis methodology and to searchers in the biomedical field may forget es of the Medical School and to one major There have been other changes. The - in apply this knowledge to understand why that human stories populate the landscape graduate school course. This is followed by tegration between medical and graduate some bladder cancer metastasizes aggres- of what they consider primarily a research 3 to 4 years of graduate study, which is sup- schools is now better, partly because we sively and why some is relatively benign. problem to be tackled from the bench. For plemented by an ongoing clinical tutorial are blessed with a number of accomplished Similarly important are the large number me, this program and the Department of and by a final 13-14 month “Clinical Year.” educators and administrators, MDs and of faculty members working across mul- Pathology and Cell Biology serve as remind- PhDs, who watch over students and make tiple disciplines, who serve as teachers and ers that scientific work becomes all the more The MSTP at Columbia is a close collabora- sure that all progress on schedule. We do role models. Beyond the bench, weekly critical and satisfying in the context of the tion between faculty and students with the not presume that we have reached perfec- student seminars in our program provide human lives. Mike Badgley is a second year single aim of training outstanding young tion, but, with nearly 500 applications a an integrated and friendly environment graduate student. physician-scientists who will lead to coming year for 15 places, we are confident that for dialogue and keep us aware of current generations of biomedical research. our MSTP program is one of the best in research spanning various fields. These Students in the Med-into-Grad Program the country.

22 23 Cell Biology Women in Pathology

An MD-PhD student perspective by Kimberly Robinson By Heidrun Rotterdam, MD provide a realistic time frame to complete into the world of translational research In my office, there ing faces of 18 women and 15 men. How an uncompromised doctoral dissertation. that I had sampled during medical school. hangs an old photo- did we get from there to here (there being Training at Columbia fosters the interdis- graph of the class of a past of struggling individuals, here being ciplinary relationships physician scientists As I think about selecting a clinical spe- 1922 of the School of a present of groups of curious and happy sustain throughout their careers to merge cialty, I find pathology to be the most inter- Medicine of Colum- women who, more or less successfully, bal- clinical responsibilities with research. esting and amenable to my research goals. bia University, still ance career and private lives)? I have observed graduates of the MD/PhD in its original frame, Walking onto campus to begin my studies program return to this department after brown wood, faded A list of residents that passed through our in 2007, I was pleasantly surprised at the residency to continue their career as facul- and scratched and department starting in 1967 reveals some diversity and camaraderie I observed in ty; this is likely due to the way the depart- probably with its interesting statistics: During the 20 years ment encourages translational research by original glass. I rescued it from certain de- before our most recent chairman, Dr. Mi- Kimberly Robinson and her advisor Gil Di Paolo the program. From welcoming my fam- ily during orientation and the White Coat establishing provisions for physician scien- struction one late evening when the garbage chael Shelanski, arrived, there were 19 fe- Physician scientists are expected to integrate Ceremony to stories shared over various tists to have bench space and time for clini- collector was about to take it together with male residents and 65 male residents (M/F clinically relevant research with proficient tantalizing ethnic foods during MD/PhD cal responsibilities. As a student in this piles of discarded office refuse. The brittle ratio 3.4). After his arrival in 1987, the ratio patient care. This integration is underscored Fall and Spring dinners, program admin- department I have been nurtured, chal- paper is cracked in many places but through changed remarkably: during the next 20 in the Medical Scientist Training Program istrators have personally made me feel lenged, and endowed with the skills I need. the resulting geographic haze, I see 85 stern years, between 1987 and 2007, there were 57 at Columbia University administered comfortable and valued. As an aspiring I have no doubt that the faculty, staff, and faces, 79 male, 6 female, all looking straight female residents and 74 male residents (M/F through the Department of Pathology and researcher, I chose the program to engage administrators will continue to provide an ahead, lips tightly closed, a faint smile here ratio 1.3) and between 2007 and 2011 there Dr. Frantz was the first ever female intern Cell Biology. The program, directed by Dr. in a rigorous clinical curriculum, and I was excellent training environment for bud- and there but a real smile with parted lips were 18 female residents and 15 male resi- in the Department of Surgery at Presby- Michael Shelanski, ultimately aims to pre- not disappointed. During the pathophysi- ding physician scientists in years to come. only on one face, a woman in the lower right dents (M/F ratio 0.83). Yes, we have come a terian Hospital from 1922 to 1924 when pare the next generation of leaders in medi- ology course at P&S, I was fascinated by corner. I don’t know who she is, but I think long way. We have come to be equals as far she advanced to surgical instructor. She cal research. Students matriculate into the the knowledge and passion shown by so Kimberly Robinson did her undergraduate she is right to smile: she is one of very few as opportunity and achievement are con- branched out into surgical pathology College of Physicians & Surgeons and then many faculty members from this depart- degree in biochemistry at Andrews Univer- women allowed to study medicine, to grad- cerned. But is there something unique we, (then a division of surgery) in 1926 and enter the Graduate School of Arts and Sci- ment. Many of these individuals practice sity. She came to Columbia in 2007 and is uate and perhaps to have a career thereafter. the women in pathology, can offer? remained a surgical pathologist and re- ences to complete degrees in both schools in medicine and do basic research- a combi- currently doing her PhD work titled, “The You’ ve come a long way, baby. searcher for the rest of her life. She was a 7-8 years. Dr. Shelanski, as well as assistant nation that I wish to emulate. I later joined role of phospholipase D1 in trafficking and In 1957, when Virginia Frantz was offered thyroid specialist, wrote the first descrip- directors Drs. Ron Liem and Patrice Spit- the department as a graduate student to processing of amyloid precursor protein” with I do recognize one of the other female faces: the “Elizabeth Blackwell Award”, given to tion of insulin-producing tumors of the alnik, have structured the training plan to enjoy the equally stimulating immersion Dr. Gil Di Paolo. Dr. Virginia Kneeland Frantz, who became women for distinguished service in medi- a well known pathologist; her office on the pancreas, was the first to use radioactive cine, research and teaching, she considered 14th floor of Vanderbuilt Clinic is still there, iodine to demonstrate and treat metastatic rejecting the award, because it identified somewhat altered by repeated renovations, thyroid cancer (both with Dr. Whipple) her as a ”female” doctor. “I am not a medi- From the Archives: Some Recent Awards but still of the same shape and size. Dr. and wrote the AFIP fascicle on pancreatic cal oddity”, she is quoted as having said, Frantz does not smile, she looks as stern as tumors in 1959. before she accepted it. On the topic of med- most of her male colleagues. Remember, ical education, she remarked that ”teach- the first women in our profession needed to Not all Ivy League Medical Schools joined ing is much more philosophical specula- constantly prove that they could be as seri- the initial group of 13. Harvard Medical tion than formal pedagogy, much more art ous and devoted to their profession as men. School did not open their doors to women than science, much more fun than work”. until World War II and women physicians So perhaps it is this element, we the women As I pursue my inquiry into women in were considered an oddity for quite some in pathology, can contribute to our profes- pathology and descend to the “Archives time thereafter. When I applied for a resi- sion: to infuse the science, the service, the & Special Collections” in the basement of dency in Internal Medicine at Massachu- teaching with beauty and with joy. the Long Health Sciences Library I come setts General Hospital in 1968, I was told across some remarkable details related that I had three strikes against me: I was a Dr. Heidi Rotterdam was the last trainee to Dr. Frantz and my photograph of her woman, I was a foreigner, and I was mar- in surgical pathology of Dr. Raffaele Lattes graduation. Indeed, 1922 was the first year ried to a non-physician. “People like you go from 1974 to 1975. She returned to CUMC that the School of Medicine of Colum- into pathology”, someone suggested. And as an attending pathologist in July 1991 bia University graduated women. In 1917, so I did. And I have no regrets. and has been here since. three years into World War I, due to a drop in male applicants, 13 medical schools, Where are we today? As I look at our sur- among them the College of Physicians and gical pathology sign-out schedule there Surgeons of Columbia University, broke are 8 women and 11 men. Our Director Dr. Michael D. Gershon received the 2008 Dr. Joan Witkinwon the coveted Dr. Janet Sparrow won the Research to Prevent their all-male admission policy and al- of Surgical Pathology is a woman, our de- Masters Award for Sustained Achievement in Balmfolk Award for teaching excellence. Blindness Senior Scientist Award. partment administrator is a woman. As I Digestive Science. lowed women to apply. Six women among 85 graduates seems a small number but it look at the list of residents and fellows for represents a big step forward. the year 2011-2012, I see the mainly smil-

24 25 Oral Pathology Facts and Figures From the Archives: Around the Department

By David J. Zegarelli, D.D.S. By Joann Li, Department Administrator and Our Neurogenetics Laboratory Steve Russo, Deputy Department Administrator My first recollection of oral pathology be- mind in pathology. She remained for 10 gins way back in the 1960s when I was an years sharing equal responsibility. In 1987, The Department of Pathology had undergraduate dental student in the College been without a chairman for a period of of Dental Medicine of Columbia University. Our laboratory was then separate from the over three years. It was housed in 35,000 Two part-time professors, later my mentors surgical pathology laboratory – and we ran sq. ft. of antiquated office and laboratory and friends, Drs. Lester Cahn and Melvin it as a private practice under the auspices space in the College and Vanderbilt Clini- Blake, taught the 48 hour undergradu- of the College of Dental Medicine and the cal Buildings. It had 67 full-time faculty ate course in oral pathology. It was classic Department of Pathology. For a variety of members who performed 25,000 surgi- clinical – radiographic – microscopic oral administrative reasons it became incum- cal diagnoses per year, and its medical pathology. They initiated my interest in bent in the mid 1990s to align the laborato- residency program accommodated 16 resi- oral pathology and during my senior year ry service into the surgical pathology labo- dents. Research grant funding to the de- I chose oral pathology as a specialty. I will ratory and an important event occurred. partment was less than $400,000 per year. not forget Dr. Cahn arriving every Wednes- I broached the subject with Dr. Shelanski day wearing his Bowler hat and carrying his and he welcomed the oral pathology prac- Today, after 25 years, the Department of silver-tipped cane. Dr. Donald King offered tice into surgical pathology. This further Pathology & Cell Biology possesses nearly me a residency position in general patholo- cemented the relationship of the dental double the space with 63,000 sq. ft. of ex- gy stating that all subspecialties of patholo- school with the department of pathology tensively renovated laboratories and offices gy are based in general pathology. That was and from my vantage point we appear to across several CUMC buildings. We cur- enough for me to commence my residency work well with one another. rently have over 93 full-time faculty (both at CUMC on July 1, 1969 – although there clinical and basic science), 126 Research were no full time oral pathologists then in Dr. Pulse left CUMC and moved to Florida. Officers, 19 Fellows, 21 Residents, 60 -Offi Members for the Laboratory: From left to right: Jiesheng Lu (Associate Research Scientist), Dr. Naini, this institution. Eventually, we increased our staff through cers of Administration and 120 SSA Union Sindu Krishna (Senior Staff Associate) and Maryam Shirazi (Postdoctoral fellow). Employees. In 2011, we processed and re- the help of Dr. Shelanski to 3 full time oral Grants administration staff One year into my residency I learned that pathologists. This faculty increase allowed ported on over 55,000 surgical specimens, 2 of my 3 years had to be spent under the us to develop a 36 month Oral and Max- 60,000 cytologies, 239 autopsies, 2,500 The Department’s Antique Microscope, stored illofacial Pathology Residency Program consults and nearly 40,000 physician re- in dusty splendor in Mike Shelanski’s office, is direct auspices of a full time oral patholo- a Powell and Lealand monocular made about gist. Consequently, I chose an oral pathol- supported by the Department of Hospi- views of nearly 6.7M laboratory clinical lab 1870. It may have been Delafield’s. ogy residency program at the College of tal Dentistry but centered entirely in the tests. The Department consistently ranks Dental Medicine of S.U.N.Y. at Buffalo, Department of Pathology. This newly es- in the top 5 nationally among Pathology NY. I shuffled up to Buffalo for 2 years tablished program contributed one of our Departments (1st in New York and New spending an almost equal amount of time 3 current full time oral pathologists. Dr. England) in NIH funding. In 2011 there between the oral pathology residency at Angela Yoon, our first resident graduate, were 59 ($22million) NIH funded grants. S.U.N.Y.A.B, and, being a resident in gen- passed her boards shortly after completing This is all achieved with an overall operat- eral pathology at Roswell Park Memorial the program and currently serves as an as- ing budget of approximately $75M. Institute. Remembering Dr. King’s words sistant professor. She has been joined by Dr. From left to right Josie Salcedo, Steve Russo, Irene D’Silva and Frances Antonetty – I completed more than 90 autopsies dur- Elizabeth Philipone, a recent graduate of the Against a background of uniform excel- Dr. Ann-Judith Silverman ing my 3 year program. LIJ program. Together, we perform teach- lence, the Department is widely recog- ing, research and patient care activities. nized for its clinical expertise in the diag- During the Spring of 1972 I was offered 2 nosis and understanding of diseases of the full time positions in oral pathology. One, kidney, brain, liver, and female reproduc- I could be the eighth oral pathologist in tive tract. One of many books from the department Buffalo, or, the first and only full time oral pathologist at CUMC. The choice was a no The clinical laboratories at the Presbyteri- brainer and I returned to N.Y.C. and Pres- an, Harkness, CHONY, Milstein, and Al- byterian Hospital and began teaching, re- len sites provide a wide array of STAT and search and patient care activities. The Oral routine services 24 hours per day/7 days Diagnostic Biopsy Service was established per week and a broad menu of routine and on July 1, 1972 and continues to flourish– specialty testing during regular weekday having processed more than 150, 000 sur- working hours. A wide array of point-of- gical oral pathology specimens. I worked care (POC) testing services is supported at solo for 18 years and finally a second oral all Hospital sites and throughout the Am- pathologist came aboard – Dr. Carla Pulse bulatory Care Network. Clinical consulta- tion services by our MD, PhD, and MD/ – a University of Tennessee graduate with Dr. Jay Lefkowitch...yes, I know where everything is. View of the Bridge from the PhD physicians, laboratory directors, fel- a distinctive southern charm and an astute Cell Division. A work of art by Dr. Julie Canman new labs in the Black Building. Continued on back cover

26 27 Facts and Figures

lows, and residents are available at all times to health care providers to provide support Pathology & Cell Biology NIH Research Funding $30,000,000 in clinical decision making and to resolve laboratory testing issues. $25,000,000 line Trend $20,000,000 Divisions in Anatomic Pathology include Surgical Pathology, Autopsy, Neuropathol- $15,000,000 ogy, Obstetric/Gynecologic Pathology, Cy- topathology, Hematopathology, Immuno- $10,000,000 pathology, and Renal Pathology. Practice $5,000,000 sites are The College of Physicians and Sur- geons of Columbia University, Presbyteri- 0 1987 1990 1995 2000 2005 2011 an Hospital, and Vanderbilt Clinic. Frozen section diagnoses are provided in the Mil- stein Pavilion and the Allen Hospital. The Clinical Revenues divisions collectively process and report on $35,000,000 more than 100,000 specimens each year. $30,000,000 29 $25,000,000 23.4 24 24.6 The Department contributes significantly 21.8 to the educational mission of the Colum- $20,000,000 19 bia University Medical Center, with strong 17 $15,000,000 13.5 14.4 ACGME approved pathology residency 10.8 and fellowship training programs, with $10,000,000 9 6.8 8 leadership roles in medical student educa- $5,000,000 tion, and with leadership positions in grad- 0 uate biomedical education and the MD- 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 PhD Medical Scientist Training Program. Departmental faculty members are con- sistently recognized with teaching awards into Grad” grant award from the Howard the only clinical and basic science depart- from the medical school and several of Hughes Medical Institute. ment in the university. The rise in NIH them have been elected to the prestigious funded research from less than a half mil- Glenda Garvey Teaching Academy. Final- Twenty-five years ago there was one NIH lion dollars in 1987 to last year’s total of ly, building on the success of a new course research grant. The arrival of Mike Shel- $22 million is almost constant. Looking in graduate education aimed at encourag- anski brought a cadre of researchers and a at the graph we can see the impact of the ing PhD students to pursue medically-rele- huge bump, going to about a dozen NIH Clinton initiated doubling of the NIH bud- vant research, members of the Department grants in that first year and rising to the get in 1998 and the fallout of the end of that were recently awarded a prestigious “Med current 59 grants in the department. It doubling process in 2003. also created a designation of Pathology as

Anniversary Edition 1987-2012

Chairman http://pathology.columbia.edu/ Dr. Michael L. Shelanski Our Diagnostic Services The Department offers a very broad range of Delafield Professor of Pathology Senior Proofreader expertise and diagnostic services. We are avail- Pathology and Cell Biology Ms. Casey Schadie able for consultation at the following locations. Editor Dr. Richard H. Kessin Web: www.pathology.columbia.edu Professor The Newsletter normally follows the activities of Email: [email protected] Pathology and Cell Biology our administrative staff, lists new Honors, and Laboratory services: Design and production new grants that have been awarded. We describe 1-800-653-8200/1-212-305-4840 Richard V. Miller the work of new faculty. These standard News- Print Services letter subjects will return in the fall issue. Administrative Services: 1-212-305-7164