Alumnus Speaker at the 2005 MSTP Retreat

Neil Chi , M.D., Ph.D.

I graduated from the Medical Scientist Training Program at Northwestern University in 2002 and will bethe Alumni Speaker at the 2005 MSTP Retreat on August 14-15, 2005.I graduated from the Medical Scientist Training Program at Northwestern University in 1998 and am the Alumni Speaker at the 2005 MSTP Retreat on August 14-15, 2005. Currently I am an Assistant Professor of Medicine in the Division of Cardiology at University of California, San Francisco .

Research Interests

Cardiovascular diseases remain the leading cause of morbidity and mortality in the United States and developed countries. Heart failure is a world-wide public health problem that causes one million hospitalizations per year and 350,000 deaths annually. Additionally, every year, approximately 450,000 individuals in the United States die suddenly of cardiac arrhythmias due to a variety of etiologies ranging from myocardial infarctions to cardiomyopathy. However, our understanding of the cellular and molecular mechanisms involved in cardiomyopathy and sudden death have remained relatively limited in the past. Through further understanding of these molecular events, our hope is that these findings will translate into novel therapeutic options for patients with heart failure and cardiac arrhythmias.

Utilizing other vertebrate animal models, such as mice, chicks, and zebrafish, to study these cardiovascular disorders has recently allowed extensive dissection of these molecular pathways as well as integration of these mechanisms with pathophysiology and overall cardiac phenotype. Our research is aimed at advancing our understanding of the molecular mechanisms involved in heart failure and sudden death through utilizing the zebrafish genetic model system. Recent studies on zebrafish mutants with similar phenotypes to other human diseases are providing immediate insight into genes linked to human diseases ranging from blood disorders to cardiovascular diseases. Thus, this approach has proven itself a rapid and reliable system for providing new mechanistic insights into well-described human diseases especially cardiovascular disorders. We have already identified several zebrafish mutants in which many display phenotypes similar to human heart failure and cardiac arrhythmias.

The cloning of the revealed critical genes of these zebrafish heart failure and cardiac arrhythmia mutants will have significant impact on gaining a molecular entrance for inherited as well as acquired human cardiovascular diseases. Not only may these genes be used as genetic markers for screening human patients for genetic etiologies of heart failure and cardiac arrhythmias, but they also may provide potentially novel therapeutic interventions for these particular cardiovascular diseases.

Representative Publications

Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors. Chi, NC and Karliner, NS. Cardiovasc Res. 2004 Feb 15;61(3):437-47.

Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3. Milewski RC, Chi NC , Li J, Brown C. Development. 2004 Mar;131(4): 829-37.

Trends Genet. 2002 Jan;18(1): 41-7. Related Articles, Links Getting your Pax straight: Pax proteins in development and disease. Chi N and Epstein JA.

Functional domains in nuclear import factor p97 for binding the nuclear localization sequence receptor and the nuclear pore. Chi, NC and Adam SA. Mol Biol Cell. 1997 Jun;8(6):945-56.

Different binding domains for Ran-GTP and Ran-GDP/RanBP1 on nuclear import factor p97. Chi, NC, Adam EJ. J Biol Chem. 1997 Mar 7;272(10):6818-22.