GRADUATE PROGRAMS IN CLINICAL CHEMISTRY DEPARTMENT OF CHEMISTRY CLEVELAND STATE UNIVERSITY

The graduate programs (master’s and Ph.D. programs) in Clinical Chemistry are dynamically integrated programs merging the fields of biomedicine, clinical diagnosis, and analytical chemistry. The instructional and training components are carried out by clinical chemistry faculty in the Department of Chemistry at Cleveland State University, with active participation of the clinical laboratories at the Cleveland Clinic and MetroHealth Medical Center, involving many doctoral clinical scientists from these, as well as other, medical centers in the Cleveland area. Given below are summary descriptions of the masters programs in Clinical Chemistry (section A) with more in-depth descriptions of the curriculum and participating faculty (sections B and C, respectively).

A. Summary of Master’s Program in Clinical Chemistry

The curriculum of the master’s program in Clinical Chemistry is designed to give an in-depth education in clinical laboratory science as described in detail in section B. There are multiple faculty members who actively contribute to the master’s program in clinical chemistry (see section C). Focal faculty members in the program include four CSU faculty members in the clinical chemistry/biochemistry division and two faculty members at the major Cleveland medical facilities of the Cleveland Clinic and MetroHealth Medical Center. These faculty members contribute significantly to the teaching and research aspects of the program. In addition to these core faculty members, there are approximately 20 doctoral clinical scientists that give lectures in their areas of expertise. Finally, there are ten other faculty members in the Department of Chemistry at CSU (in addition to the four in the clinical/biochemistry division) for whom master’s students can work in doing thesis research (thesis option). The ten other CSU faculty members also teach graduate elective courses.

Students can select either a coursework or thesis track in the master’s Clinical Chemistry program, depending on the goal of the student. For employment opportunities in the technical field, a thesis master’s degree is highly recommended. This is because competitiveness for positions in the biotechnology, biomedical, pharmaceutical, and other industrial laboratories, as well as technician positions in academic/medical research laboratories is enhanced with prior laboratory experience. The master’s program in Clinical Chemistry does not usually apply for specific jobs in the clinical laboratories (such as hospital labs) since the medical technicians positions require a medical technology degree. A master’s program in

1 Clinical Chemistry will be applicable to students who are already a medical technologist (or have graduated with a medical technology degree) in order to further their education, with the opportunity to move into a supervisory position in the clinical laboratory. The master’s program in Clinical Chemistry is also applicable for students interested in medical school, as the courses in the program give in-depth instruction in medical subject areas. As stated above, a thesis option is recommended in order to obtain positions in industry or research technician positions.

B. Program Curriculum - Requirements for the Master’s Program in Clinical Chemistry

1. Listing of Course Requirements for Graduate Programs in Clinical Chemistry The course requirements and options in the master’s programs in Clinical Chemistry are given in Tables 1 and 2, respectively. CSU is on a semester system with courses offered in the fall and spring semesters. Internship courses are also offered in the summer semester (with approval of the Co-Director of Clinical Chemistry). Each fall and spring semester is fifteen weeks, with each semester credit being approximately one hour of class time per week.

Table 1 Requirements of the Coursework Master’s Program in Clinical Chemistry

Course Credits per course Clinical Chemistry I (CHM 651) (Fall, Year 1 or 2) (4) Clinical Chemistry II (CHM 652) (Fall, Year 1 or 2) (4) Biotechnology Techniques (CHM 655) (Spring, Year 1) (4) Advanced Biochemistry I (CHM 653) (Fall, Year 1) (4) Advanced Biochemistry II (CHM 654) (Spring, Year 1) (4) Internship in Clinical Laboratory I (CHM 756) (Fall or Spring, after Year 1) (6) Special Topics in Clinical Chemistry (CHM 750) (Fall and Spring, after Year 1) (1, 2 courses) Graduate Chemistry Elective (Fall or Spring, after Year 1) (3-4) Clinical Chemistry Seminar (CHM 759)* (Fall or Spring, any year)______(1)* Total 32

* Suggested if the graduate chemistry elective is only 3 credits. Taking this course will meet the 32 credit requirement for the master’s degree in this case. Alternatively, another course can be taken to meet the minimum 32 credit requirement.

2 Table 2 Suggested Curriculum for Thesis Master’s Chemistry Program with Concentration in Clinical Chemistry

The following are the requirements for a thesis option of master’s with suggested courses for a concentration in Clinical Chemistry:  14 credits of courses [one course in each of the three of seven course categories (analytical, clinical, biochemistry, inorganic chemistry, organic, physical, environmental)]. It is suggested for a concentration in Clinical Chemistry that one course be in the Clinical Chemistry division (either CHM 651 or CHM 652), two courses be in the biochemistry division (CHM 653 and CHM 654), and one course be in the analytical division (this will total 15 to 16 credits)  2 credits of chemistry seminar (CHM 695)  16 credits of any combination of Advanced Chemistry Lab (CHM 679), Annual Research Report (CHM 690), and MS Thesis (CHM 699)

Depending on the goals of the student, taking another course in the Clinical Chemistry division and one or two courses in Special Topics in Clinical Chemistry (1 credit each) is encouraged in the thesis option to get a more comprehensive coverage of the clinical chemistry field. This, however, does increase the total credit hours.

2. Description of Curriculum in the Graduate Clinical Chemistry Programs a. Overview The curriculum of the master’s program in Clinical Chemistry is designed to give an in-depth education in clinical laboratory science. Required clinical courses include two core clinical chemistry courses (CHM 651/751 and CHM 652/752), four (two for coursework masters) special topics courses in clinical chemistry (CHM 750), and one internship course (CHM 756). This approach allows for the systematic and comprehensive coverage of the field of Clinical Chemistry. It is the goal of the program to give the graduate student comprehensive and rigorous instruction in disease processes, relating this to disease diagnosis. The curriculum also gives instruction in the methodology, instrumentation, and general laboratory procedure issues related to the clinical laboratory. This is done in the graduate laboratory course in biochemical and molecular biology techniques (CHM 655/755), through elective courses, and the internship course (CHM 756). Students get practical training in the clinical laboratory in the latter course. Other required courses include two graduate biochemistry courses (CHM 653/753 and CHM 654/754), a graduate chemistry elective, and two chemistry seminars (CHM 695/795) (for Ph.D. program only). Finally for the doctoral program, an extensive research experience in scientific investigation is obtained through dissertation research (CHM 899), in which the student gets a focused and in-depth research experience in biomedical/clinical areas, sophisticated analytical methodologies, and/or therapeutic agent development; culminating in the defense of a dissertation.

3 b. Lecture/Laboratory Courses in Clinical Chemistry The two core Clinical Chemistry courses (Clinical Chemistry I and II; CHM 651/751 and CHM 652/752, each 4 credits, offered fall semesters on a rotating basis) are taught from an organ-based approach, in which the use of the laboratory in the diagnosis of diseases of each particular organ (or physiologic) system is covered. There is instruction in anatomy, physiology, and the biochemical basis of the disease, presented as background to discussing the use of the laboratory in disease diagnosis. These two courses combine for a two semester sequence in clinical chemistry, covering the following topics: renal, liver, cardiovascular, acid-base, hemolytic diseases; hypothalamus-pituitary axis and diabetic endocrine disorders; lipids and lipoproteins; laboratory statistics; and other topics.

The four Special Topics in Clinical Chemistry courses (CHM 750; 1 credit each; offered at least once a year) systematically cover clinical topics that are not covered in the core courses, including: tumor markers, hematology, molecular diagnostics, and other topics. See Table 3 for the rotating topics. These courses are organized by a CSU Clinical Chemistry faculty member and taught by a team of Ph.D. and M.D. lecturers from Cleveland area medical centers.

Table 3. Special Topics in Clinical Chemistry Courses Topic Core Subjects Clinical Endocrinology Molecular Diagnostics Tumor Markers Hematology

The Biotechnology Techniques course (CHM 655/755; 4 credits) consists of a one hour lecture and five hours of lab a week. The course covers various molecular biology, protein electrophoresis, and immunoassay techniques topics; going over theory and giving students laboratory experience in biomedical research techniques.

c. Clinical Chemistry Internship Courses Practical training in the clinical laboratory is obtained through an internship course. Internship in Clinical Chemistry I (CHM 756; 6 credits) is a course in which students rotate through the clinical laboratory at Cleveland area medical centers. The course is a six-week (eight hours per day, four days a week) rotation through the clinical laboratory, as well as having a half-day discussion session each week.

4 Students are trained in the instrumentation used in the clinical laboratory and in the general operation and management of the clinical laboratory. Students learn the principle of operation of the instruments, observe the medical technologists performing the test, and may in some cases run duplicate, non-reported samples. Students learn the principles of the methods and instrumentation in the discussion sessions, through reading the instrument and procedure manuals at each station, and through discussion with laboratory personnel. During the time spent at each station, the student will have time to observe and learn the procedures of quality control and quality assurance that are implemented within the clinical laboratory (such as the use of control samples in quality monitoring, noting corrective actions taken when control values are beyond acceptable limits, and learn maintenance procedures). Students also obtain instruction in sample processing and in precautions needed to maintain sample integrity. Quality control is covered in the discussion sessions and is also observed in practice in the rotation through the various stations in the clinical laboratory. Students learn about a variety of tests and the clinical use of these tests throughout their rotation and in the discussion sessions. Students may also be assigned evaluation and/or developmental projects which give a more in-depth experience with the instrumentation and methods evaluation/development procedures.

The course is organized by a CSU co-director in conjunction with Ph.D. heads of clinical laboratories at the participating Cleveland medical centers, primarily CCF and MetroHealth Medical Center. The clinical chemists at the particular medical center oversee the rotations of the student at clinical laboratory. The discussion sessions led by CSU faculty cover multiple topics of importance in the clinical laboratory.

The Internship in Clinical Chemistry II course (CHM 757; 6 credits) is an optional second course that can be taken for additional specialized training in an area of the clinical laboratory that interests the student.

d. Other Lecture and Seminar Courses A year of graduate biochemistry is also required (Advanced Biochemistry I and II, CHM 653/753 and CHM 654/754; 4 credits each). It is taught by a CSU faculty member. One elective graduate chemistry course (3-4 credits) is also required. An optional Clinical Chemistry Seminar course (CHM 759, 1 credit each, can be taken multiple times) gives additional exposure to Clinical Chemistry through presentation of case histories and clinical seminars at local medical facilities. A one year sequence of Chemistry Seminar (CHM 695/795; 1 credit for each seminar course) is required (doctoral Clinical Chemistry and thesis master’s programs only). Internal and external faculty/scientists give seminars on their research in this seminar course.

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e. Course Catalog Descriptions The summary descriptions of the courses are given in Table 4.

Table 4. Summary Descriptions of Required/Optional Courses in Clinical Chemistry Program

CHM 651/751 Clinical Chemistry I (4 credits). Laboratory diagnosis of kidney, liver, and hemolytic diseases. Instruction includes physiology and pathophysiology in conjunction with laboratory testing for the above diseases. Laboratory statistics is also covered.

CHM 652/752 Clinical Chemistry II (4 credits). Laboratory investigations of disorders in acid-base balance, lipid and carbohydrate metabolism, and endocrine functions. Biochemical markers of myocardial infarction. Case studies.

CHM 653/753 Advanced Biochemistry I (4 credits). Chemistry of proteins, carbohydrates, and lipids; immunology and AIDS. Enzymes and energetics of metabolic reactions.

CHM 654/754 Advanced Biochemistry II (4 credits). Metabolism of nitrogen-containing compounds, vertebrate metabolism, neurotransmission, nucleotides, and nucleic acids, DNA processes, RNA synthesis and processing, protein synthesis, gene expression, and cancer.

CHM 655/755 Biotechnology Techniques (4 credits). Techniques of immunoassays and techniques of isolation, manipulation, and analysis of proteins/nucleic acids are covered. Includes both lecture and laboratory.

CHM 756 Internship in Clinical Chemistry I (6 credits). Students rotate through the clinical laboratory at Cleveland medical centers, as well as prepare for and participate in discussion sessions. Topics trained/instructed in include; instrumentation, quality control, and diagnostic uses of various testing methodologies. Students may be assigned evaluations and/or development projects for a more in-depth experience. Management issues of the clinical laboratory are also addressed.

CHM 750 Special Topics in Clinical Chemistry (1 credit). Discussion of topics in clinical chemistry and related clinical disciplines. May be repeated for credit with change of topic.

CHM 695/795 Clinical Chemistry Seminar (1 credit). Speakers give seminars on various chemistry and biomedical research areas.

CHM 757 Internship in Clinical Chemistry II (6 credits). Students rotate through the clinical laboratory at Cleveland medical centers in testing areas not covered in the first internship course (CHM 656/756) .

CHM 759 Clinical Chemistry Seminar (1 credit). Students attend clinical seminars at Cleveland area medical centers.

6 C. Overview of Faculty Participating in the Program There are several categories of faculty that participate in the program, as indicated in Table 5.

Table 5. Program Faculty and Lecturers Categories Faculty Category Faculty Names Activity in Program CSU Faculty (Clinical Anderson (Co-Director), Wei Teaching and research Chemistry/Biochemistry (Co-Director), Kalafatis, Zhou Division) Clinical Faculty Ip and Wang Teaching and research Clinical Laboratory and other 19 lecturers Teaching Clinical Lecturers CCF Faculty 32 faculty Research CSU Faculty (Other Divisions) Bayachou, Ball, Berdis, Guo, Teaching (elective courses) and Gogonea, Masnovi, Sun, Su, research Turner, Xu

7 Table 6 lists the research areas of the program faculty for whom students have the opportunity to do dissertation research. Students in the Ph.D. program can choose to work for faculty at either Cleveland State University or the Cleveland Clinic Foundation (mutual consent of student and faculty member). Students in the masters program can choose to work for faculty at in the Department of Chemistry at Cleveland State University only (mutual consent of student and faculty member).

Table 6. Research Interests of Program Faculty

Cleveland State University: Department of Chemistry David Anderson, Ph.D., DABCC HPLC and mass spectrometry of proteins, proteomics, pharmacokinetic studies David Ball, Ph.D. Cryogenic matrix isolation IR, ab initio calculations Mekki Bayachou, Ph.D. Biosensors and bioelectrochemistry applied to cytochrome p450, nitric oxide synthase, and DNA interactions (with anti-tumor agents, antibiotics, regulatory proteins) Anthony Berdis, Ph.D. Chemical and biological studies of DNA replication, DNA repair and nucleoside metabolism. Development of small molecule inhibitors of DNA polymerization and repair pathways to potentiate existing chemotherapeutic agents. Valentin Gogonea, Ph.D. Computational chemistry, molecular modeling of proteins and macromolecules, including nitric oxide synthase and hydrogenase, and high density lipoproteins Baochuan Guo, Ph.D. Mass spectrometry of proteins, DNA, and bile acids; mass spectrometric immunoassays Michael Kalafatis, Ph.D. Biochemistry of blood coagulation and thrombosis; biochemistry of cancer, therapeutic agents for thrombosis and cancer John Masnovi, Ph.D. Mechanistic organic and organometallic chemistry; cytochrome P450, EPR, NMR, kinetics Bin Su, Ph.D. Medicinal chemistry, developing new drugs for ER+ and Her2 breast cancers Xue-Long Sun, Ph.D. Bioanalytical, pharmaceutical and medicinal chemistry. Glyco- affinity techniques applied to proteomics, glycomics, and targeted drug delivery; cytomimetic antithrombotics; cellular chemistry, glycoarrays. John Turner, II, PhD Biomedical imaging, multivariate analysis and spectroscopy applied to analysis of sub-micron architecture of tissues and cells, biomaterial implants, artificial cell scaffolds, and diagnosis of pre- cancerous lesions Robert Wei, Ph.D., DABCC Environmental pathology, free radicals Yan Xu, Ph.D. Capillary electrophoresis, immunoassays, and mass spectrometry in bioanalysis; pharmacokinetic and pharacodynamic endpoints of novel therapeutic agents; development of anti-tumor drugs Aimin Zhou, Ph.D. RNAse L biochemistry in infectious diseases, cancer, cardiovascular disease, diabetes, inflammatory conditions, apoptosis and cell signaling. Disease marker discovery.

Cleveland Clinic Foundation : Department of Clinical Pathology Sihe Wang, PhD, DABCC HPLC, LC-MS, ICP-MS, cardiac markers, kidney function, nutrition assessment, and TDM and clinical toxicology, vitamin D

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Cleveland Clinic Foundation: Lerner Research Institute Alex Almasan, Ph.D. Genotoxic stress-induced signals for cell control, cell death, and survival. DNA damage in tumors, Apo2L/TRAIL in apoptosis signaling and cancer therapy

Tatiana Byzova, Ph.D. Cell adhesion molecules (integrins) in thrombosis, vascular biology and cancer, vascular endothelial growth factors, angiogenesis, extracellular matrix including bone matrix proteins Kathleen Berkner, Ph.D. Vitamin K-dependent protein carboxylation Martha Cathcart, Ph.D. Human monocyte activation, inflammation, regulation of NADPH oxidase generation of superoxide anion, lipid oxidation, expression of 15-lipoxygenase, signal transduction, regulation of monocyte chemotaxis to MCP1 Guy Chisolm, III, Ph.D. Lipoprotein oxidation in inflammation and atherosclerosis, intracellular signaling events of apoptosis in vascular cells, genetically altered mouse models of vascular disease John Crabb, Ph.D. Mass spectrometry in proteomics, age-related macular degeneration, primary open angle glaucoma Carol de la Motte, Ph.D. Hyaluronan-mediated platelet-endothelial interactions in inflammation; role of hyaluronan in angiogenesis associated with inflammatory bowel disease; hyaluronan recruitment of endothelial progenitor cells in lung repair Paul DiCorleto, Ph.D. Vascular endothelial cell gene expression and regulation in atherosclerosis. TNF-a Signaling, role of Homeobox Gene HOXA9, MAP Kinase Phosphatase-1 in EC signaling Donna Driscoll, Ph.D. Post-transcriptional regulation of gene expression, selenocysteine Serpil Erzurum, MD Airway inflammation and host defense, reactive oxygen and nitrogen species in lung disease, pulmonary vascular endothelium and angiogenesis, asthma, pulmonary hypertension Maria Febbraio, Ph.D. Role of CD36 in atherosclerosis, macrophage biology, diabetes, fatty acid metabolism Paul Fox, Ph.D. Translational control of inflammatory gene expression, endothelial cell migration, macrophage iron metabolism Ram Ganpathi, Ph.D. Clinical pharmacology and experimental cancer chemotherapy Saikh Jaharul Haque, Ph.D. Cytokine-mediated cell signaling in health and disease, particularly in allergic inflammation and brain cancer Vincent Hacall, Ph.D. Underlying cellular mechanisms that initiate matrix synthesis; internal matrix structures differing from normal HA matrices; mechanisms whereby inflammatory cells (mast cells, eosinophils, neutrophils, monocytes/ macrophages) adhere to and degrade abnormal HA matrix in response to regulation/progression of inflammatory processes. NIH Program of Excellence in Glycosciences Stanley Hazen, MD, Ph.D. Mass spectrometry in biomedical research. Mechanisms of atherosclerosis; leukocyte peroxidases; nitric oxide and reactive oxygen species; oxidant injury in asthma and other inflammatory diseases; cardiovascular genetics

9 Jane Hoover-Plow, Ph.D. The plasminogen dependent proteolysis in leukocyte migration in inflammation and stem cell mobilization; Plasminogen and lipoprotein(a) interactions in the development of thrombosis; Genetic determinants of thrombosis; Role of extracellular matrix Emilin proteins in thrombosis . Donald Jacobsen, Ph.D. Cardiovascular disease, homocysteine metabolism, endothelial cell function, cobalamin and folate biochemistry Sadashiva Karnik, Ph.D. GPCR structure-function, signal transduction, cell growth. Ang II receptor function and cell death of Ang II expressing cells. Chromation remodeling changes induced by Ang II receptors Xiaoxia Li, Ph.D. Signal transduction in innate and adaptive immunity Thomas McIntyre, Ph.D. Lipid mediators and their role in apoptosis, inflammation, platelet function, and aging Richard Padgett, Ph.D. Mechanisms of RNA splicing in vivo and in vitro Edward Plow, Ph.D. Molecular mechanisms of cell adhesion and migration. Integrins, platelets, protease receptors, plasminogen, fibronection

Jun Qin, Ph.D. Biomeolecular NMR spectroscopy, protein-protein and protein- nucleic acid interactions, signal transduction Robert Silverman, Ph.D. Innate defense against viruses and cancer. Antiviral mechanisms of RNase L, role of RNase L in the biology of prostate cancer, broad- spectrum antivirals that activate RNase L, XMRV infections in prostate cancer Roy Silverstein, MD Vascular biology, including thrombosis, angiogenesis, atherosclerosis, and inflammation; CD36 and TSR- containing proteins Jonathan Smith, Ph.D. The pathobiology and genetics of atherosclerosis and atrial fibrillation, and the mechanisms involved in reverse cholesterol transport. ApoA1 variants, pathways in the cholesterol uptake by macrophages. Microarrays and bioinformatics.

George Stark, Ph.D. Signal transduction pathways involving interferons, STATs, NFKB, p53 and TGF ß ; methods for forward genetics in mammalian cells Dennis Stuehr, Ph.D. Structure and biochemistry of nitric oxide synthases and related enzymes Bruce Trapp, Ph.D. Cellular and molecular biology of myelination, demyelination, and dysmyelination Qing Wang, Ph.D. Microarray analysis, genetics and molecular biology of diseases, gene expression, developmental biology of the heart and blood vessels Qingyu Wu, MD, Ph.D. Regulation and function of corin. Corin converts pro-atrial natriuretic peptide (ANP) to active ANP. SNPs corin variants have low biological activity, genetic variants may impair corin function and contribute to hypertension and heart disease in patients

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