School of Medicine
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Postdoctoral Research Fellow, Cardiovascular Medicine
Bio My long-term goal is to learn, develop and design frameworks to implement ?Precision Medicine? based on the ?rare? and ?common? genomic variants. Particularly, I am enthusiastic to construct global precision medicine basis to help individuals with diabetes, insulin resistance and cardiovascular comorbidity.
After completing my master?s degree in human genetics, I was attracted by the fact that early onset coronary artery disease (CAD) manifest as a genetic subtype of the common type of CAD. In collaboration with Dr. Arya Mani and Dr. Richard Lifton, experts in Mendelian forms of CAD (Yale University), and Dr. Reza Malekzadeh, a pioneer of cohort studies (Tehran University), I contributed to the genetic analysis of families with early onset CAD and metabolic syndrome. We identified DYRK1B as a causative gene (co-first author; N Engl J Med; 2014).
During my PhD thesis, I worked on exome data of Mendelian/monogenic disorders that have been sequenced at Yale Genome center to filter them for rare and pathogenic variants. Also, I used RNA-Seq to sequence the transcriptome of human skeletal muscle biopsies from the carriers and non-carriers of the DYRK1B mutation. I also applied LFQ-MS (label free quantification- tandem mass spectrometry) to address changes in the proteome of DYRK1B mutants in both human muscle biopsies and in vitro models. Through these studies I gained an experimental and conceptual framework for high-throughput data analyses focusing on the networks of metabolic pathways for insulin resistance.
After completion of Ph.D. thesis at Yale University, I was enthusiastic to be trained deeply on the genetic basis of diabetes and insulin resistance. Navigating through leading institutes, I found Stanford University an ideal place for this training; because here at Stanford Cardiovascular medicine, Dr. Gerald Reaven, a pioneer of insulin resistance, along with Drs. Thomas Quertermous and Joshua Knowles had developed the multicenter cohort for a GWAS of insulin resistance by direct measures of insulin sensitivity including ?clamp-based? measures of insulin resistance. This group had just identified and validated a common SNP (rs1208, 803A>G, K268R) in N-acetyltransferase 2 (NAT2) as insulin resistance variant. In this innovative training and career development, I am taking part in defining the role of Nat1 (mouse ortholog of NAT2) in the global and liver specific knockout mice. We have already profiled ?OMICs changes in the Nat1 global knockout mice with insulin resistance and extensively analyzed the data with promising finding on possible mechanism of mitochondria substrate availability and cholesterol biosynthesis.
As we are pursuing the functional genomic studies of human NAT2/mouse Nat1, I wrote a chapter book tilted? The Human Arylamine N-Acetyltransferase Type 2 Gene: Genomics and Cardiometabolic Risk?. To write this chapter book I had the supervision of Dr. Knowles and Dr. David Hein (a pioneer of NAT2 studies in cancer predisposition and pharmacogenetics). This chapter is included in an erudite monograph ?Arylamine N-acetyltransferase in Health and Disease?. The link advertising the book published by World Scientific Publishing is:
During postdoctoral fellowship, I am involved in the joint project of Stanford-Merck on functional characterization of lipodystrophy-like genes identified through GWAS of glycemic traits (fasting insulin, HDL and WHR adjusted for BMI). This study has opened up new possibility and insight to target peripheral adiposity and insulin resistance. We extensively have been studying one of these promising targets in the transgenic mice and in the data from human cohorts. Currently, I am writing the manuscript of these finding and soon we submit it for publication.