Research interests

With recent resource and technology development, biology has entered a new data-driven phase in the 21st century. The research interests of this lab are computational genetics and systems biology, focusing on algorithm development, data integration, and software implementation. With the advent of new DNA sequencing technologies, it is a particularly challenging and exciting time now to do such computational work, as more and more biological data are being generated at an ever-accelerating speed.

Research projects, active

In reverse chronological order

» DNA Repair, Mutations and Cellular Aging

Genome instability, driven by DNA damage, is now generally considered a hallmark of aging, which is underscored by increasing evidence for DNA damage as a driver of aging-related disease, most notably cancer and neurodegenerative disease. However, what remains lacking is specific insight into the genetic control and molecular mechanisms that link DNA damage and genome instability to aging and longevity in humans. This program project is organized around three major research questions that remain in this field: (1) the key genome maintenance genotypes that control human aging and longevity; (2) the genetic and molecular basis of DNA damage-driven aging; and (3) How DNA damage and its molecular sequelae affect cell fate diversity in aging.

This research program project is supported by a grant from NIH/NIA.

» Comparative genomes of longevity

Mammalian species differ dramatically in their aging rates, but mechanisms responsible for these differences are unknown. This program project will identify mechanisms responsible for more efficient DNA repair and higher cancer resistance in long-lived rodents. This knowledge will enable the development of interventions to extend the human lifespan and delay the onset of age-related diseases.

This research program project is supported by a grant from NIH/NIA.

» Genetic variant-based drug discovery targeting conserved pathways of aging

Aging is an important risk factor for most common human diseases. In this multi-component project, we will test a new approach for developing therapies for these diseases. Rather than focusing on individual diseases, we explore genetic differences between successfully aged, healthy centenarians and control individuals with no family history of extreme longevity.

This research project is supported by a grant from NIH/NIA.

» Complex biology of resilience to Alzheimer’s disease risk

Centenarians are a population enriched with AD resilience, as many maintain normal cognition throughout their lifespan or significantly delay the onset of cognitive decline, despite chronological age being the major risk factor for dementia. In this comprehensive, cross-disciplinary study, we aim at building predictive molecular models of cognitive resilience based on genetic and high-dimensional molecular data collected in centenarians.

This research project is supported by a grant from NIH/NIA.

» Systems biology of organismal aging

Aging is a fundamental biological process accompanied by a general decline in tissue function and increased risk for many diseases. Instead of a passive, entropic process of deterioration, it is subject to active regulation by signaling pathways and transcription factors. In this project, using C. elegans as the model organism, we will develop innovative systems and computational biology approaches to construct regulatory networks of aging and identify emergent properties about the molecular mechanisms of aging.

This research project is supported by a grant from the Irma T. Hirschl Trust.

» Human non-coding variants

People’s genomes differ at tens of millions of sites, and interpreting how this variation affects phenotypes and disease risk is extremely challenging. Most disease-associated variants lie outside of protein-coding regions. We are developing highly innovative computational approaches to determine which non-coding variants contribute to differences in organismal phenotypes and disease risk.

This research project is supported by a grant from NIH/NHGRI.

Research projects, completed


» Brain and behavior in 22q11.2 deletion syndrome

The International Consortium on Brain and Behavior in 22q11.2DS is a collaborative R01 of 22 institutions, with one genomic and four phenotyping leading sites. The collaboration combines genomic with neuropsychiatric and neurobehavioral paradigms to advance the understanding of the pathogenesis of schizophrenia and related phenotypes. The project as a whole will be an unprecedented international initiative to examine a common deletion associated with schizophrenia and elucidate its genomic and behavioral substrates. Beyond the potential for yielding a better understanding of a severe manifestation of 22q11.2DS, the results will help identify pathways leading to schizophrenia in the general population in a way that will inform novel treatments.

This research project is supported by a grant from NIH/NIMH.

» Congenital heart defects of 22q11.2 deletion syndrome

About 65% of 22q11.2DS patients have a heart defect such as tetralogy of Fallot – a form of conotruncal heart defects (CTDs) – and 35% have a normal heart. It is not clear why CTDs only occur in some, not all, of 22q11.2DS patients. Lack of such knowledge is an important problem, because, without it, acquiring the ability for prenatal diagnosis and intervention of CTDs among 22q11.2DS carriers is highly unlikely. Our project is to unravel the genetic basis for this phenotypic heterogeneity. By finding the genetic basis for CTDs in 22q11.2DS individuals, this study may pave the way for prenatal diagnosis and intervention of CTDs among 22q11.2DS carriers.

This research project was supported by a grant from the American Heart Association.

» Systems biology of human aging

For reasons significant to individuals and the society as a whole, human aging is of great interest not only to the academic community but also to medicine and the public in general. However, despite much research progress made over the years, it still remains a poorly understood biological process. To gain novel insights, we use a systems-biology approach to analyze aging-related genes in the context of biological networks.

This research project was supported by a New Scholar Award from the Ellison Medical Foundation.

» Computational analyses of gene regulation: a next-gen sequencing approach

Gene expression in living cells is under strict spatial and temporal control, and its dysregulation is the direct cause of many human diseases. The primary focus of research in my lab is gene expression and its regulation, for which we take an integrated approach to study the following aspects on the whole genome scale:

  • gene expression profiles,
  • transcriptional regulation of gene,
  • expression epigenetic mechanisms and long range control of gene expression,
  • gene copy number variation.

The biological system currently under investigation is breast cancer metastasis, a complex multi-step process during which tumor cells spread from the primary tumor mass to distant organs. To study the genetic and biochemical determinations of this deadly aspect of cancer progression, we analyze various microarray and sequencing profiles to discover its regulatory sub-networks, DNA binding of key regulators, and copy number variations during the progression.

This research project was supported by a grant from NIH/NLM.