Our laboratory focuses on applying combinations of computational modeling, bioinformatics, and in vitro and in vivo experimentation (systems biology approaches) to solve problems related to cancer, cardiovascular and ocular diseases. System biology and multiscale modeling has emerged as powerful methodologies to integrate the data from a variety of sources and at different levels of biological organization spanning multiple spatial and temporal scales .
Systems Biology of Cancer
The overarching goal of the Systems Biology Laboratory is to apply modern methods of biomedical engineering to better understand the mechanisms of cancer and to significantly advance treatments for this devastating disease. Cancer cells invade into healthy tissues and co-opt these tissues into promoting tumor growth and metastasis. They use multitude of ways to evade therapeutics by adapting to drugs making them ineffective. To control and conquer the disease, the applications of modern quantitative methods are absolutely necessary; our laboratory is at the cutting edge of the cancer systems biology research. The research in the laboratory uses a combination of experimental and computational approaches. We investigate cancer at different levels from genes to proteins to tumor, and the whole body. We look into the ways the factors that stimulate tumor growth (e.g. growth factors) signal to the interior of the cell, and how cancer cells communicate with their neighbors such as immune cells and vascular cells. We develop and test novel drugs to treat different types of cancer. Our research focuses on the following areas:
- Fundamental studies of cancer biology to better understand how different cells interact to cause cancer metastasis
- Identification of novel molecular drug targets for different types of cancer – Drug discovery including therapeutic peptide agents to inhibit tumor growth and metastasis
- Immuno-oncology aimed at turning patient’s immune system to targeting cancer cells
Recent promising results from studies on immune checkpoint blockade therapies as well as adoptive transfer of engineered T-cell have energized the researchers, clinicians and pharmaceutical companies. Our lab has focused on development of multiscale computational models to investigate the interaction of the immune cells with cancer cells in the tumor microenvironment to better understand the important factors in a strong anti-tumor immune response and to propose novel therapeutic approaches for cancer immunotherapies.
Systems Biology of Peripheral Arterial Disease
Peripheral arterial disease (PAD) is a manifestation of atherosclerosis that causes impaired blood flow to the extremities. Peripheral artery disease affects 12 to 15 million people in U.S. and its prevalence is comparable to that of coronary artery disease. Therapeutic angiogenesis is a strategy that promotes blood vessel growth to improve tissue perfusion. We use bioinformatics, computational modeling, and in vitro and in vivo experimentation to solve problems in PAD. Using bioinformatics approaches, we studied protein networks that determine processes of angiogenesis, arteriogenesis and inflammation in PAD. We also investigated drug repurposing for potential applications as stimulators of therapeutic angiogenesis.
Using computational modeling approaches, we investigate signal transduction pathways and build 3D models of angiogenesis using differential equations-based and agent-based approaches. This research is performed in collaboration with Dr. Brian H. Annex, Director of Cardiology at the University of Virginia.
Discovery of Anti-Angiogenic and Anti-Lymphangiogenic Therapeutic Peptides
Using bioinformatics methods, our laboratory discovered over a hundred of novel anti-angiogenic peptides. We then embarked on experimental in vitro and in vivo studies testing their activity under different conditions. We investigated structure-activity relationship (SAR) doing point mutations and amino acid substitutions and constructed biomimetic peptides derived from their endogenous progenitors. Some of the peptides exhibit anti-lymphangiogenic properties, in addition to anti-angiogenic. We have demonstrated efficacy of selected peptides in mouse models of breast, liver, lung, and brain cancers, and in mouse and rabbit models of age-related macular degeneration and diabetic macular edema. With our clinical collaborators, we are aiming at translating these discoveries to the clinic.
Inhibition of angiogenesis (neovascularization) and vascular leakage in wet age-related macular degeneration and diabetic macular edema
We apply anti-angiogenic peptides as therapeutic agents in several animal models of age-related macular degeneration and diabetic macular edema. This research is carried out in collaboration with Dr. Peter A. Campochiaro, Professor of Ophthalmology, The Wilmer Eye Institute. We are also collaborating with Dr. Jordan J. Green of Biomedical Engineering who is developing sustained delivery vehicles using nanotechnology for long-term delivery of the peptides.