Front Line news from the Department of Pharmacology and Experimental

Community Pride Honoring the behind-the-scene supporters Research support comes innovative projects forward, as well as ventured into new areas of research. in many forms including In 2006, department chairman Howard grants from the National E. Gendelman, M.D., hosted the first Institutes of Health (NIH) Community Pride in Neuroscience Lecture and Dinner to recognize the and other federal agencies, outstanding support and generosity of not-for-profit foundations, these individuals and to recognize out- and industry sponsors. standing scientists in the field of neu- roscience. Now, in its fourth year, the two-day event kicks off with a lecture by But, what happens to research ideas an international scientist, followed by when such funding is not available? meetings of faculty and students and Thanks to the generosity of a quiet a dinner honoring the distinguished group of individuals, the Department scientist and community members. of Pharmacology and Experimental This year the lives of lifelong Nebraska Neuroscience at the University of Nebraska Medical Center has moved see Community Pride pg 6

Two Neuroscience Centers In June two neuroscience center’s established in 1997 under Howard were approved. The Center for E. Gendelman, M.D. The Center Neurodegenerative Disorders and the for Integrative and Translational Center for Integrative and Translational Neuroscience, directed by Howard Neuroscience will both explore the S. Fox, M.D., Ph.D., is the link be- causes of neurodegenertive diseases to tween basic science discoveries and improve diagnostics and potential drug translational implementation in the therapies. clinic. “It is our vision to make UNMC a world leader in the treatment of The Center for Neurodegenerative neurodegenerative disorders such as Disorders, directed by Tsuneya Parkinson’s and Alzheimer’s diseases,” Ikezu, M.D., Ph.D., evolved from the Dr. Gendelman said. Both centers former Center for Neurovirology and Neurodegenerative Disorders, see Neuroscience Centers pg 3

Volume 1, Issue 1 | October 2009 Letter from the Chair

It seems like yesterday that I walked into the halls of the University of Ne- braska Medical Center with hope, promise and some dollars to launch a new research program in the . What has happened in just over a decade was honestly beyond my wild- est dreams. A department focused on brain research was not imagined let alone being among the top in the nation. Achievements at an inter- national level in Alzheimer’s and Parkinson’s disease, stem cell biology, nanomedicine, drug abuse and HIV disease research were also not imag- ined but are true today. Our publications have appeared in high-level journals and are among the most cited in neuroscience research. Patents abound and are now being translated into real inventions to benefit mankind. The recruitments of Howard Fox, M.D., Ph.D., and Shilpa Buch, Ph.D. have solidly set the stage for even further growth. Their wisdom, enthusi- asm and team spirit raised our bar again. Can we go even further? Yes we can! A new biotechnology company, Neuropel Pharma Inc., was founded and is designed to take our inventions and develop them for clinical use. Tsuneya Ikezu, M.D., Ph.D., and his team discovered a new gene targeted for Alzheimer’s therapeutics. Can we take an incurable disease and find Newsletter new treatments? We can and we will! October 2009 Volume 1, Issue 1 Not to be undercut, our education program in pharmacology is the best This newsletter is produced by the it has been in nearly a decade. Department of Pharmacology and Experimental Neuroscience An early vaccine for Parkinson’s disease spells a formidable combination University of Nebraska Medical of science, technology and educational developments. Can we see clini- Center cal applications? We can and we will! There is much that lies before us. Can we meet those challenges? With Editor: Robin Taylor our partnerships together, yes we can and yes we will! Assistant Editor: We developed this program with you. You have made dreams come true Lesley Gendelman and even more will certainly be realized these next few years. Cures, and Photography: at the least, better treatments for diseases are within our grasp. Malone & Company, Birrell Signature Photography, James Thank you for your support and I look to our future and the future of our Roubal, Lennart Mucke, M.D. and mission with excitement and awe in finding cures to so many devastating Robin Taylor diseases. For additional printed copies, contact: Department of Pharmacology and Experimental Neuroscience 985800 Nebraska Medical Center Omaha, NE 68198-5800 Howard E. Gendelman, M.D. (402) 559-4035 Chair, Department of Pharmacology and Experimental Neuroscience www.unmc.edu/pharmacology Larson Professor of Internal Medicine

Front Line | 2 New Research Dollars Howard S. Fox, M.D., Ph.D., and Their work, in conjunction Shilpa Buch, Ph.D., recently joined with others in the department, bringing with them the department, multiple millions of dollars in Na- set the stage for tional Institutes of Health research understanding grants. commonalities of neurodegenerative Each of them is carrying out pathways as they important work examining the relate to other mechanisms of neurodegenera- disorders such as tion and potential treatments for Alzheimer’s and protecting the brain. Parkinson’s Disease, In addition, they jointly and means to research on how illicit drugs prevent or treat affect brain pathology, these debilitating and the disorders conditions. Growth in total grant dollars for the resulting from HIV infection. Department of Pharmacology and Experimental Neuroscience

Neuroscience Centers continued from pg 1 were built from major research gains develop world–class scientists and radiology, medicine and surgery, in in neuroscience made at UNMC. health care professionals of the highest order to rapidly move new discoveries integrity, compassiont and competence. out of the lab and into the clinic. “The development of “Neuroscience is now at the stage neurodegenerative research and The Center for Neurodegenerative where we can move our laboratory education at UNMC is one of the Disorders will succeed the findings up through molecular, cell primary goals of our strategic extraordinary successful Center for culture and animal models to people, plan,” said Dr. Ikezu. Currently, Neurovirology and Neurodegenerative so we can alleviate the burden of there is no organizational structure Disorders and will direct the these neurodegenerative illnesses in place at UNMC to stimulate program to be more focused on as soon as possible,” Dr. Fox said. neurodegenerative disorder research basic and therapeutic research on “Advances in technology now allow on a campus–wide basis. The Center neurodegenerative disorders with close relationship and partnership us to diagnose diseases of the brain for Neurodegenerative Disorders will with the Center for Integrative and earlier and more exactly. It is at enhance the research infrastructure, Translational Neuroscience at UNMC. these early stages that treatments provide an administrative home for would likely be most effective.” interdepartmental graduate and The Center for Integrative and postdoctoral training and be a conduit Translational Neuroscience will focus between the academic and private on translational medicine and take the sectors. There is an increasing demand fruits of neurodegenerative research for innovative research and education from the bench to the bedside. in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, Dr. Fox said the center brings together , and amyotrophic basic research faculty with clinicians lateral sclerosis. This is necessary to in , , pediatrics,

Volume 1, Issue 1 | October 2009 Parkinson’s Research

In 2000, the Center for Neurovirology and minted clinical investigations have demonstrated that the Neurodegenerative Disorders was not known for approach is reasoned and viable. research in Parkinson’s disease. Eric Benner, an The work, published in many major scientific journals, M.D./Ph.D. student, had an idea to develop a serves as a cornerstone as our scientists look for new ways Parkinson’s vaccine. Unfortunately, funding was to refine the vaccine to change the landscape of this and not available in this area of research. Although other incurable diseases that affects so many millions of the initial studies failed, community-supported Americans. funds allowed a vaccine program for Parkinson’s Collaborations with neurologists at the University to begin. of Alabama and here at UNMC are underway with the hope of bringing actual vaccine trials The dream to establish a Parkinson’s vaccine continued with to patients within the next two years. the mantle taken over by graduate students Ashley Reynolds and David Stone. Over the past eight years working under Although a vaccine is a long way off, Phase I clinical trials the guidance of Howard Gendelman, M.D., and R. Lee to be performed here at UNMC are now being considered. Mosley, Ph.D., this dream has become a recognized reality. Pre-clinical studies have shown proof of concept and newly

Translational Research

Michele Aizenberg Ansari, M.D., These works, jointly developed by and parts of Asia. The value of having is among UNMC’s most active Michael Boska, Ph.D., Irena Kadiu, long-acting medicines made available and successful neurosurgeons. Ph.D., Howard E. Gendelman, M.D., through the works of UNMC scientists Zhiya Ma, Ph.D., Huangyu Dou, Ph.D., cannot be overstated. A single injection She began a brain tumor program and Dr. Aizenberg, are used in rodent of a therapeutic drug given once per where none existed in Nebraska and in models of disease and in a new brain month is being developed for clinical a time frame of less than a year. tumor repository developed by Dr. trials (Dou et al. Blood 2006; Dou et al. Aizenberg. Journal of Immunology 2009; Nowacek Patients are attracted from all over the et al, Nanomedicine 2009). region and beyond to seek her surgical The hope is that in the near future such and medical skills in what many research activities can be translated The HIV research program here at consider the most devastating of all to humans, who now have perhaps a UNMC is already world-recognized and diseases, malignant glioblastoma. less than a two year prognosis after is advanced greatly by strides in basic diagnosis. and applied research. The research being conducted between Dr. Aizenberg and scientists in the Department of Susan Swindells, M.B.B.S., Terry Stephen Bonasera, M.D., Ph.D., Pharmacology and Experimental K. Watanabe Professor and Assistant Professor, Internal Neuroscience is nothing less than Medical Director , UNMC’s Medicine, Geriatrics, focuses on revolutionary. Advances in proteomic how the brain normally ages. and bioimaging are leading to new HIV Clinic knows first hand the potential advances in diagnostics, importance of compliance to Behaviors that are important for a staging and therapeutic monitoring antiretroviral therapy for HIV/ loved one to remain independent and include research into antibody- AIDS. and at home include physical targeting of tumors and novel drug activity, eating, drinking, resting, and delivery strategies. This is especially a concern in patients socializing. who abuse drugs and also in the developing world such as in Africa

Front Line | 4 Alzheimer’s Research

The Alzheimer’s disease scientific achievement with notable the subject of several new research awards and international talks seen reports (Kiyota et al, Molecular Therapy research program led by in recent months. Drugs targeting 2009 and PLoS One, 2009). Tsuneya Ikezu, M.D., Ph.D., TTBK1 for clinical applications, and recently identified a new gene the development of a high-throughput The laboratory is now characterizing called tau-tubulin kinase 1 drug screening system using robotic even more potent genes for the technologies are now operative. treatment of Alzheimer’ disease. (TTBK1) that is a potential target for new therapies for Active investigations in the Ikezu These activities are part of on- Alzheimer’s disease. laboratory use recombinant DNA going studies at the Center for technology commonly called gene Neurodegenerative Disorders. This therapy for Alzheimer’s includes the Center will focus on Alzheimer’s and A patent was filed for the genetic DNA means to target anti-inflammatory other neurodegenerative disorders to sequence and a transgenic mouse cytokines, chemokine mutants, and bring scientific inventions to people as made that expresses TTBK1. This gene growth factors that can improve quickly as possible. Led by Dr. Ikezu, the demonstrates age-dependent memory memory and learning in affected new center includes Steven Bonasera, impairments and was published in two people. M.D., Libin Cui, PhD., Howard E. articles (Sato et al. J. Gendelman, M.D., R. Lee Mosley, Ph.D., 2006 and J. Neuroscience 2008). These new treatments will also affect and Jialin Zheng, M.D. There is worldwide interest in this disease and were also

Many investigators combine such In this way, we hope to find specific events into broad measurements treatments that will maximize people’s called “Lifespace.” These methods independence during aging. provide only a snapshot of a person’s lifespace at a given time. The Bonasera lab studies lifespace in mouse models of aging and in translational clinical studies of human aging. They use mobile phones to collect data describing an individual’s total activity, in-home location, and in-community location on a continuous basis. This approach to studying lifespace is inexpensive, non-invasive, temporally and spatially precise, and highly valid.

We also can continuously study analogous behaviors in large mouse populations. Thus, investigators at UNMC are in an ideal position to identify specific pharmacological or therapeutic interventions to preserve an individual’s functional behavior, quickly test these interventions in mice, University of Nebraska Medical Center and then evaluate human clinical Durham Research Center and populations for identical measures. Durham Research Center II

Volume 1, Issue 1 | October 2009 Community Pride Honorees 2009

2006 2008 Lennart Mucke, M.D. Edward Robinson

2007

Frances and Louis Blumkin, Howard E. Gendelman, Howard E. Gendelman, M.D. and Carol Swarts, M.D. M.D., Harriett Singer and Steven Jacobson, Ph.D. Donald Gilden, M.D. Bruce Ransom, M.D., Ph.D.

Community Pride Honorees of past Community Pride in Neuroscience Lecture and Dinners: continued from pg 1 2006 residents, Edward and Lida Robinson, will be honored by The support of community members Louis and Frances Blumkin began James Roubal, and Lennart Mucke, M.D., will be honored a new area of research at UNMC into Parkinson’s disease and led to for his work in neurological diseases. several publications and grant submissions to the National Instituts of Health.

The Robinsons, through their contributions and devotion Scientist Steven Jacobson, Ph.D., chief of the viral immunology section to friends and community, have generously given hope in the National Institute of Neurological Disorders and Stroke at the to countless millions suffering from neurodegenerative NIH, whose efforts continue to define the role of human in diseases. chronic progressive neurologic diseases.

Dr. Mucke, director of the Gladstone Institute of 2007 Neurological Disease at the University of California, San The support of UNMC alum Carol Swarts, M.D., enabled the depart- Francisco since its establishment in 1998, has been a leader ment to establish the laboratory of emerging neuroscience research and fund exciting, high risk projects. One of three female graduates in in the study of Alzheimer’s disease and . the class of 1959, Dr. Swarts continues to support the place that “gave her the opportunity of a lifetime.” “Community support is the life blood of any successful program,” said 2008 honoree Donald Gilden, M.D. Bruce Ransom, M.D., Ph.D., was honored for his work on the physiol- ogy and function of glial cells and on the pathophysiology of neural Dr. Gendelman said, “The continued behind-the-scenes injury. Dr. Ransom is the founding chairman of the Department of Neu- community support will propel the department and UNMC rology at the University of Washington School of Medicine and founder to become a world leader in neurodegenerative disorders. and editor-in-chief of the journal Glia. Their support continues to amaze me; I cannot thank them 2008 enough.” Omaha philanthropist Harriett Singer’s longtime support and faith for neuroscience research came at a time when seeing a world-class program was simply a dream.

Donald Gilden, M.D., was honored for his work in clinical neurology, multiple sclerosis, acute and chronic infections of the nervous sys- tem and virus latency in the . Dr. Gilden, Louise Baum For donor information, contact the University of Nebraska Professor and chairman of the Department of Neurology at the Univer- Foundation at 402-502-0300; http://www.nufoundation.org. sity of Colorado Health Sciences Center, marveled at the outpouring of community support in Omaha for medical research.

Front Line | 6 Education UNMC Pharmacology and Experimental Neuroscience (PEN) faculty are highly regarded for their research contributions in the battle against neurodegeneration result- ing from HIV infection, Alzheimer’s and Parkinson’s diseases and amyotrophic lateral sclerosis.

A lesser-known but equally or perhaps more important PEN faculty endeavor is the dissemination of knowledge and expertise to graduate and biomedical students at UNMC and elsewhere throughout the world. PEN faculty currently direct and teach several courses that are key components of the curricula of medical, allied healthcare students are instructed that PEN graduate students are pharmacy and allied health professions by PEN faculty on the fundamentals of performing cutting-edge research on students, and in courses that provide the how drugs work and how they are used in how to use nano-formulations systems didactic component of graduate training patients to alleviate and suffering. to improve the delivery of drugs to the in neuroimmune pharmacology. These brains of Alzheimer’s, Parkinson’s and include work here in Nebraska as well Under the editorial guidance of Drs. HIV-AIDS patients as well as discovering as teachings in China and Russia. Tsuneya Ikezu and Howard Gendelman, new ways to diagnose, stage, and treat PEN faculty contributed to the publication these diseases. Other PEN students are Two years ago, the department undertook of a new textbook in neuroimmune investigating mechanisms responsible the task of enhancing its educational pharmacology that has literally created for increases in the incidence of stroke mission by recruiting a new faculty a new scientific discipline. This text is and brain damage in patients with member with expertise in pharmacology used here at UNMC and at medical chronic conditions like diabetes. teaching. Dr. David McMillan, vice-chair for schools around the world to train professional education, brought enthusiasm and doctors who will With all this exciting activity going and innovative instructional methodology develop novel therapies to confront a wide on in education, it will not be long that have already had an impact on the array of neurodegenerative disorders. before PEN’s achievements in teaching next generation of Nebraska’s healthcare attract just as much attention as professionals. Medical, pharmacy and Dr. Keshore Bidasee, the department’s its highly regarded research. vice-chair for graduate education, notes

Promotion and Tenure Graduates Shilpa Buch, Ph.D. Tsuneya Ikezu, M.D., Ph.D. Edward Arvisais Professor (tenure) Professor (tenure) Sugato Banerjee Pawel Ciborowski, Ph.D. Huangui Xiong, M.D., Ph.D. Clara Chao Associate Professor Associate Professor (tenure) Dawn Eggert Nicholas Floreani Howard S. Fox, M.D., Ph.D. Vivek Gautam Professor (tenure) Megan Montgomery Awards Scientist Laureate New Investigators Silver ‘U’ Award Howard E. Gendelman, M.D. James Haorah, Ph.D. Johna Belling Larisa Poluektova, M.D., Ph.D. Brenda Morsey Distinquished Scientists Lana Reichardt Daniel Monaghan, Ph.D. Postdoctoral Scholar Robin Taylor Jialin Zheng, M.D. Gurudutt Pendyala, Ph.D.

Volume 1, Issue 1 | October 2009 COLLEGE OF MEDICINE 985800 Nebraska Medical Center Omaha, NE 68198-5800

ADDRESS SERVICE REQUESTED

This publication is available online

Visit unmc.edu/pharmacology to share this newsletter and other UNMC publications with friends and colleagues.

Department of Pharmacology and Experimental Neuroscience

1 Community Pride in this Honoring the behind-the-scenes supporters and the work of outstanding scientists 4 Parkinson’s Research issue Developing a vaccine for Parkinson’s disease 5 Alzheimer’s Research Identifying a new gene

Volume 1, Issue 1 | October 2009