The work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human virus. KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells.
We use the premier model plant species, Arabidopsis thaliana, and real world plant pathogens like the bacteria Pseudomonas syringae and the oomycete Hyaloperonospora parasitica to understand the molecular nature of the plant immune system, the diversity of pathogen virulence systems, and the evolutionary mechanisms that influence plant-pathogen interactions. All of our study organisms are sequenced, making the tools of genomics accessible.
Cellular and molecular basis of the mucociliary clearance system in the airways of the lung. Our focus is on the regulation of mucin secretion and ciliary activity at the cell and molecular levels.
With a particular interest in pediatric solid tumors, our lab aims to develop a mechanistic understanding of the role of aberrant or dysregulated transcription factors in oncogenesis.
We study Borrelia burgdorferi (the agent of Lyme disease) as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease.
Our research centers on understanding the
molecular basis of human carcinogenesis. In particular, a major focus of our studies is the Ras oncogene and Ras-mediated signal transduction. The goals of our studies include the delineation of the complex components of Ras signaling and the development of anti-Ras inhibitors for cancer treatment. Another major focus of our studies involves our validation of the involvement of Ras-related small GTPases (e.g., Ral, Rho) in cancer. We utilize a broad spectrum of technical approaches that include cell culture and mouse models, C. elegans, protein crystallography, microarray gene expression or proteomics analyses, and clinical trial analyses.
We study how mammalian cells activate the programmed cell death pathway and die by apoptosis. We have focused our work on identifying unique mechanisms by which this pathway is regulated in postmitotic cells such as neurons, cardiomyocytes, and myotubes, as well as cancer, senescent, and stem cells. Excessive cell death is seen in many pathological conditions such as after stroke, neurodegeneration or cardiovascular diseases. In contrast, reduced cell death is a hallmark of cancers. Therefore, discovering the mechanism by which mammalian cells regulate cell death has significant therapeutic implications.
The direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials are presently being designed to reach new understandings and therapies in cancer prevention, diagnosis and treatment.
My interests focus on developing quantiative methods to assess the relationships between exposure, dose and response. This research has examined methods for dioxins, thyroid hormone disruptors and pyrethroid pesticides.
1) Identification of critical elements of human genetic variability contributing to pain sensitivity and pathophysiological pain states, 2) identification of therapeutic targets for pain management, 3) studying molecular hierarchy of functional SNPs commonly present in human population and 4) studying the molecular mechanisms of gene expression regulation.
Our lab tries to understand viral pathogenesis. To do so, we work with two very different viruses - West Nile Virus (WNV) and Kaposi¹s sarcoma-associated herpesvirus (KSHV/HHV-8).
We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.
The Dokholyan group focuses primarily on understanding protein dynamics, more specifically on how induced changes in protein folding and aggregation lead to diseases, such as cystic fibrosis, many types of cancers, and a number of neurodegenerative diseases. The Dokholyan group focuses on several such diseases, including Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, and Huntington disease. The Dokholyan group is developing a hierarchy of molecular models, from simplified coarse-grained models to more detailed ones, to create a novel multi-scale simulation methodology. This methodology will enable simulations of large molecular complexes at the biologically-relevant time scales, thereby allowing to directly glance into processes associated with human diseases. Member of the Molecular & Cellular Biophysics Training Program.
My lab studies membrane traffic between the trans-Golgi network and endosomal organelles. This central feature of eukaryotic cell biology is important for functions of the human body; including the ability to recognize and destroy infective agents, sugar uptake in response to insulin and the proper reaction of cells to growth factors-a feature important in normal development and that is often inappropriately regulated in cancer. We have two main types of projects in the lab; characterizing protein-protein interactions important for membrane traffic and chemical genetic approach to identify compounds that regulate membrane traffic.
Mechanisms of cell cycle control by cyclin dependent kinases (CDK's) and gene expression during Drosophila development, including how transcription factors (the pRB tumor suppressor and E2F), RNA metabolism (histone pre-mRNA processing), and protein ubiquitination and proteolysis (cullin dependent ubiquitin ligases) regulate the G1-S transition and DNA replication.
The study of opioid analgesics, with particular focus on opioids that are less likely to produce physical dependence and abuse. Research in the laboratory has examined the relationship between the analgesic effects of opioid analgesics and their interaction with specific opioid receptor types. A more recent research interest includes investigations of genetically-altered mice with relevance to drug dependence and the development of models of mouse behavior for examining behavioral phenotypes related to a range of behavioral disorders.
