TRAINING PROGRAM ADMINISTRATION:

Program Director: Dr. Andrew R. Marks joined the Columbia faculty in 1997 as the inaugural Director of the Center for Molecular Cardiology in the Department of Medicine. In March 2003 he was appointed Chair of the Department of Physiology & Cellular Biophysics. He now holds professorships in both departments and is an attending physician on the cardiology service of New York Presbyterian Hospital.

Program Co-Director: Dr. Ira Tabas is Professor of Medicine and Anatomy and Cell Biology, Professor of Physiology and Cellular Biophysics and Vice-Chairman for Research in the Department of Medicine.

Associate Director for Trainee’s Development: Dr. Jaime S. Rubin, who until recently was the Acting Associate Dean and Acting Associate Vice President for Research Administration at the Medical Center, recently joined the Dept of Medicine as Director of Research Development. Dr. Rubin has long been involved in education, training, and career development of junior investigators at the Medical Center.

AREAS OF RESEARCH:

Cardiovascular Cell Biology:
Cardiovascular Cell Biology is a multidisciplinary research group consisting of both senior investigators and junior faculty. Dr. Alan Tall is head of the Molecular Medicine Division in the Department of Medicine and holds a joint appointment in the Department of Physiology and Cellular Biophysics. Other investigators within this unit include Dr. Ira Goldberg, the Director of the Division of Preventive Medicine and Nutrition and an expert on lipid metabolism, Dr. Henry Ginsberg, the head of the Clinical Research Center at Columbia also with expertise in lipid metabolism, Dr. Ira Tabas, the Vice-Chair of Research in the Department of Medicine and renowned expert in macrophage biology and atherosclerosis, Dr. Jeanine D’Armiento who studies the role of matrix metalloproteinase (MMP) in the vascular wall, and Dr. Domenico Accili, who leads the Department of Medicine’s NIH-funded Diabetes Research Unit.

Cardiovascular Biophysics:
Columbia University’s rich tradition in ion channel research is strengthened by an outstanding group of investigators studying ionchannel biophysics and membrane/cell signaling. Dr. Robert Kass has contributed greatly to the training of fellows and junior faculty incardiovascular ion channels and is recognized as an authority oncardiac ion channel function. Dr. Andrew Marks (the PI of the grant)studies intracellular calcium release channels (ryanodine receptorsand inositol 1,4,5 trisphosphate receptors) in cardiac and skeletalmuscle, and together with Dr. Steven Marx are responsible for developing sirolimus (rapamycin) for use on drug eluting stents. Dr. Marks has recently found novel compounds that fix a leak in RyR channels and ameliorate heart failure and prevent sudden cardiac death in animal models. Dr. Arthur Karlin and Dr. Steven Marx are collaborating to identify the structural basis for beta subunitmodulation of the BK channel, the large conductance calcium and voltage gated channel expressed in smooth muscle cells, responsible in large part for regulating vascular tone. Dr. Qais Al-Awqati has a long-standing interest inthe regulation of the cystic fibrosis transmembrane conductance regulator (CFTR). Dr. Steven Siegelbaum awho studies the hyperpolarization-activated cyclicnucleotide gated, cation nonselective channel (HCN) in the heart.

Genetics, Genomics, Bio- and Tissue- Engineering, Computational Biology and high-throughput screening, translational research:
This unit is includes the laboratories of W. Chung, K. Targoff, D. Accilli, R. Liebel, A. Marks , I. Tabas, and A. Gharavi. Projects include identification of novel genes responsible for heart failure, cardiac arrhythmias, nephropathy and hypertension, obesity and/or type 2 diabetes, congential heart disease and cardiomyopathies. Dr. Andrea Califano directs the High Throughput Screening Center at Columbia and is interested in using high throughput screening methods to discover therapeutic targets for cardiovascular and other diseases; Dr. Ali Gharavi, whose laboratory is focused on identifying novel genes responsible for nephropathy and hypertension, Dr. Rudy Leibel, whose laboratory is focused on identifying genes (and relevant allelic variants) related to obesity and/or type 2 diabetes in rodents and humans; Dr. Wendy Chung (Director of the Pediatric Heart Network Genetic Core and Clinical Genetics Program), whose research relates to the molecular genetics of congential heart disease and cardiomyopathies; Dr. Gordana Vunjak-Novakovic who has a strong research focus on cardiac tissue engineering; Dr. J. Thomas Bigger, a renowned clinical electrophysiology investigator, who is now performing NIH-funded clinical trials in diabetes. In addition faculty in the department use relevant model organisms including drosophila (W. Grueber) and mice (J. D’Armiento) to study development and the genetics of diseases.

Bio- and Tissue- Engineering and Computational Biology:
The group is led by a recent recruit to Columbia University, Dr. Gordona Vunjak-Novakovic, a leader in tissue engineering of the myocardium. Dr. Jeffrey Holmes runs the Cardiac Mechanics Laboratory, which is part of the Cardiac Biomechanics Group, within the Department of Biomedical Engineering. Dr. Stephane Carlier, who directs a laboratory focused on optimizing intravascular ultrasound. For students interested in cardiovascular computational biology, Dr. Ravi Iyengar (Mount Sinai), whose expertise in signaling domains and G-protein coupled receptors/signaling provides an outstanding training opportunity.

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Translational Research Group:
Dr. J. Thomas Bigger, a renowned clinical electrophysiology investigator, is now performing NIH-funded clinical trials in diabetes and also has a Roadmap Initiative. Dr. Donna Mancini, Director of the Heart Failure and Cardiac Transplant program and Marks have collaborated in demonstrating that rapamycin can prevent progression of accelerated arteriopathy following cardiac transplantation providing the only effective therapy for this major limitation on cardiac transplants. Dr. Mario Deng is developing with collaborators a non-invasive biomarker screen for cardiac transplant rejection. For those trainees working with our diabetes or atherosclerosis group (in Cell Biology Unit) a collaboration can be established with Dr. Lori Mosca, who heads Cardiology’s Preventive Health initiatives. Columbia University Medical Center has recently recruited one of the leading groups in Interventional Cardiology, who have established a large animal research facility (Skirball Center).

Special Features of the training program:
Tutorial in Cardiovascular Science- Pre-doctoral trainees meet twice monthly over a three year period for tutorials with a senior faculty member (Marks, Tabas or other faculty from the training program). Discussions are based on assigned readings of original papers, reviews and texts. Groups no larger than 10 may include post-doctoral trainees, MD/PhD and medical students.

Year 1 concentrates on basic
molecular physiology and biochemistry of the heart, including cardiac development, excitation-contraction coupling, cardiac excitability, growth regulation of cardiomyocytes, and regulation of cardiac function by neuronal and hormonal mechanisms. Included in this year are a 4-session tutorial in basic membrane biology and a 2-session tutorial in developmental cell differentiation with Dr. Qais Al-Awqati.

Year 2 integrates and extends the basic studies to explore systemic functions, including generation of cardiac rhythms, cardiac and peripheral hemodynamics, physiologic hypertrophy, and roles of the vascular endothelium and smooth muscle.

Year 3 builds on the foregoing to examine the functional abnormalities resulting in such cardiovascular disorders as heart failure, arrhythmias, and hypertension. Etiologic and epidemiologic factors, including genetic, nutritional, and infectious causes are discussed. In this year students are taken to the New York Presbyterian Hospital to see selected patients with major cardiovascular diseases to demonstrate vividly the impact on human physiology. Each student is also asked to write a review on a current topic of interest and to lead a discussion based on the review.

Combined Program Activities for Both Pre-and Post-doctoral trainees-All trainees will participate in the following activities:

• Journal Club in Molecular Cardiology. At appropriate times in their training, trainees are asked to lead such sessions. A list of sample topics reviewed in the past year is given in Appendix. This format provides excellent teaching experience for each post-doctoral fellow.

• “Frontiers in Cardiovascular Biology” is a distinguished speaker seminar series held every other month. Trainees meet with Drs. Marks and Tabas to choose and host the speakers, and there is a lunch for speaker and trainees following the seminar.

• Trainees attend and participate in an annual, one-day retreat of the Department of Physiology. In addition to formal lectures by faculty and discussions by all, there is a poster session with contributions from trainees and faculty.

• A trainee research seminar series is held every Tuesday evening. Students in the later years of their research training present their work to their peers in the absence of any faculty. A light meal is provided. We emphasize to the trainees the importance of acquiring teaching and communication skills. At appropriate times in their training the trainees are expected to make presentations and lead sessions in the activities listed above.

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