Johns Hopkins Medicine

About

What We Do

Modern genetics involves the decoding of biological information encoded in organismal genomes and how this DNA code specifies phenotypes, be they biochemical or organismal. Genetics is also concerned with elucidating how various biological processes maintain or alter this code, its mechanism of transmission across generations and its evolution. Human genetics is the specific study of these questions in humans, studies that raise new challenges both because we cannot design genetic crosses as we do in model organisms but also because we can study phenotypes unique to humans, such as mental illness. A particular focus of human genetics is to understand the molecular basis of human disease and, thus, disease pathophysiology.

Our laboratory focuses on the formulation, development and application of genetic, genomic, and computational technologies and perspectives for discovery of genes and mechanisms in a variety of complex (non-Mendelian) human diseases. Specifically, we use a variety of human patients, their families and animal models of these disorders to infer the genetic characteristics of two developmental disorders of neuronal function (Hirschsprung disease, autism) and two late age-at-onset cardiovascular disorders (hypertension, sudden cardiac death). These disorders represent the extremes of genetic action, provide us with different models of non-Mendelian inheritance and articulate the importance of gene regulatory networks in human disease.

Common human diseases, be they birth defects, diabetes, cardiovascular disease, infectious disease, psychiatric illness or neurodegenerative disease, are familial and arise from a combination of genetic and environmental factors. The familial nature of most diseases suggests an underlying genetic susceptibility, but environmental, stochastic and epigenetic factors are also critical. Additional genetic hallmarks of complex disorders are that the underlying mutations are neither necessary nor sufficient for the development of disease, and that these mutations are common in the general population. Current genomic technologies, using the human genomic sequence, comparative sequence from many other vertebrates, a genome-wide map of polymorphic sites and emerging genome-wide maps of functional elements are all critical elements of this genetic dissection and the tools of our trade.

Our overall goals are to develop a paradigm for the genetics of common disease and to assess how genomic information can be used in modern clinical medicine in the era of personalized medicine.

Lab Members

Lab Gallery

Aravinda Chakravarti

Lab Alumni

Undergraduate Students

  • Patricia Viola (2015)
  • Prakash Chakraborty (2014)
  • Linda Xu (2013-2014)
  • Kameko Karasaki (2013-2014)
  • Ashley Gelata (2014)
  • Yun Ling (2012-2013)
  • Sayar Karmakar (2012)
  • Soudeep Deb (2011)
  • Christina Valerio (2010-2011)
  • Gaurav Dhar (2010)
  • Kinjal Basu (2010)
  • Kemi Abolade (2009-2010)
  • Saurabh Vyas (2009-2010)
  • Jaclyn Lim (2008-2009)
  • Carolyn Purington (2008)
  • Naiara Barbosa (2008)
  • Ada Davidoff (2008)
  • Parichoy Pal Chowdhury (2008)
  • Abhinash Saika (2007-2008)

MS Students

  • Kameko Karasaki (2016)
  • Vatsal Agarwal (2013)
  • Anne Kirwan (2012)
  • Jacqueline Wentworth (2011)
  • Audrey Lynn (1993)
  • Jennifer Scott (1993)
  • Laura Lasher (1991)
  • Sarah Shaw (1989)
  • Tara K. Cox (1988)
  • Susan A. Slaugenhaupt (1988)
  • Thomas R. Marino (1985)
  • Judith A. Badner (1984)
  • Kenneth H. Buetow (1983)
  • Nancy J. Wahl (1983)

High School Students

  • Arjun Rao (2011)
  • Eskender McCoy (2010)
  • Fady Hijji (2008-2009)
  • Laura Pisano (2008-2009)
  • John Rodgers (2007)
  • Kelly Beym (2007)
  • Erika Yeung (2006-2007)
  • Abena Bruce (2006)
  • Ijeoma Eboh (2006)

Research

Research in my laboratory focuses on the human genetics of complex traits and disease and the use of computational and animal models of human disease. Our studies cover three broad areas, as outlined below. Specifically, we are developing the principles and methods to do genetics ‘by sequence not breeding.’ The combination of whole genome studies (using genetic markers, sequencing or expression) and phenotypic analyses of patients, their family members and controls, can now allow the detailed dissection of both rare and common complex disorders into their component genes. Hypotheses of transmission and disease mechanism can then be studied using animal models (zebrafish and mouse). We are specifically interested in developing gene regulatory networks by cell types, that is groups of functionally interacting genes and their encoded proteins, as a basis for the multigenic action and interactions in complex traits.

Hirschsprung Disease Study

An Overview

Publications

  • All trainees are highlighted.
  • Dr. Chakravarti’s full publication list can be found here.
  • Wang, H, Nandakumar, P, Tekola-Ayele, F, Tayo, BO, Ware, EB, Gu, CC, Lu, Y, Yao, J, Zhao, W, Smith, JA, Hellwege, JN, Guo, X, Edwards, TL, Loos, RJF, Arnett, DK, Fornage, M, Rotimi, C, Kardia, SLR, Cooper, RS, Rao, DC, Ehret, G, Chakravarti, A & Zhu, X 2018, ‘Combined linkage and association analysis identifies rare and low frequency variants for blood pressure at 1q31’, European Journal of Human Genetics. PMID:30262922

  • Kapoor A, Lee D, Zhu L, Soliman EZ, Grove ML, Boerwinkle E, Arking DE, Chakravarti A. Multiple SCN5A variant enhancers modulate its cardiac gene expression and the QT interval. Proceedings of the National Academy of Sciences. 2019 May 8:201808734. PMID: 31068470

  • Tilghman JM, Ling AY, Turner TN, Sosa MX, Krumm N, Chatterjee S, Kapoor A, Coe BP, Nguyen KD, Gupta N, Gabriel S. Molecular Genetic Anatomy and Risk Profile of Hirschsprung’s Disease. New England Journal of Medicine. 2019 Apr 11;380(15):1421-32. PMID: 30970187

  • He, K., Li, X., Kelly, T., Liang, J., Cade, B., Assimes, T., Becker, L., Beitelshees, A., Bress, A., Chang, Y., Chen, Y., de Vries, P., Fox, E., Franceschini, N., Furniss, A., Gao, Y., Guo, X., Haessler, J., Hwang, S., Irvin, M., Kalyani, R., Liu, C., Liu, C., Martin, L., Montasser, M., Muntner, P., Mwasongwe, S., Palmas, W., Reiner, A., Shimbo, D., Smith, J., Snively, B., Yanek, L., Boerwinkle, E., Correa, A., Cupples, L., He, J., Kardia, S., Kooperberg, C., Mathias, R., Mitchell, B., Psaty, B., Vasan, R., Rao, D., Rich, S., Rotter, J., Wilson, J., Chakravarti, A., Morrison, A., Levy, D., Arnett, D., Redline, S., & Zhu, X. (2019). Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.. Human genetics, (). PMID:30671673

How to apply

FOR PROSPECTIVE GRADUATE STUDENTS, POSTDOCTORAL FELLOWS AND OTHER TRAINEES….

I am always in the search for scientifically enthusiastic graduate students and postdoctoral fellows to join my laboratory. I find my laboratory exciting precisely because of my trainees who bring new perspectives, questions and ideas…and, of course, new interests and new personalities! Over the past 37 years, and ever since I have been a preceptor in one or more graduate and post-graduate training programs, I have been fortunate to recruit a large number (~70) of talented trainees who have taught me just as much as we have been able to teach them.

My laboratory is focused on the fundamentals of human genetics, particularly as it relates to the understanding of human disease. Our current research is focused on two disorders of the nervous system where disease onset is early (Hirschsprung disease, autism) and two disorders of the cardiovascular system where disease onset is late (sudden cardiac death, hypertension). This breadth emphasizes the gamut of human genetic mechanisms. I expect that human genetic diseases are the photographic ‘negatives’ from which the ‘positives’ of normal physiology will emerge. To do so, we successfully use both experimental and computational approaches in human genetics and genomics, as well as use model organisms to test mechanistic hypotheses emerging from gene discovery.

My philosophy has been to let trainees choose what they want to study within the confines of the broad interests and grant support of the laboratory. I do not force any of them, graduate students or postdoctoral fellows, to focus on a particular question, but do help and guide them to the major scientific questions of the day; rather, I expect my trainees to learn to think independently but to work collaboratively because this is what they will need to do when they start their careers. Nevertheless, I work with all of my trainees very closely and expect them to gain expertise in both experimental and computational approaches, and contribute to the scientific life of the lab.

Mine is not a very large lab nor one where high-throughput technologies dominate but one where genetic arguments and genetic perspectives are central: we use the tools, both small and large, necessary for answering the question at hand. For any potential PhD trainee interested in our research please apply to the Sackler Institute of Biomedical Sciences at NYU and directly to my email; postdoctoral fellows should write to me directly at least 9 months prior to an expected start. For any trainee, a visit to the lab is always a good idea.

My lab also hosts visiting international undergraduate students in the summer, and any NYU undergraduate throughout the year through a practicum. For all such students, research work in my lab can be taken for academic credit. We also host exceptional high school students who have a deep interest in human genetics.

Aravinda Chakravarti

Principal Investigator

Email

CONTACT

Center for Human Genetics and Genomics
NYU School of Medicine
Science Building
435 E 30th Street
New York, NY 10016 USA

Tel: (212)-263-8029 Fax:(646)-501-4526

For administrative questions, contact : Jessica Jaffe 

For study participation questions, contact : Hirschsprung@nyulangone.org

For laboratory questions, contact: Hanna Berk-Rauch 

LOCATION

       CAMPUS MAP