Harvard Catalyst Profiles

University of Wales, Cardiff	BSc	01/1981	Zoology
Temple University, Philadelphia	MA	07/1986	Molecular Genetics
Temple University, Philadelphia	PhD	09/1991	Molecular Genetics
Baylor College of Medicine, Houston		01/1993	Molecular Evolution
University of Texas, Houston		01/1993	Molecular Evolution
Smithsonian Museum of Natural History, Washington, D.C.		01/1994	Molecular Evolution
Baylor College of Medicine, Houston		01/1995	Genomics

My group performs computational biology using a systems approach to deliver interventions through an understanding of processes underlying disease.

In Africa, we exploited what we found in the analysis of genomics into the focused development of health research capacity
In USA I now translate understanding of the underlying processes of disease into broadly applicable health interventions.

African Genomics and Disease
The applied global aspect of my work ha sbeen capacity development using genomics to impact health in Africa. The approach exploits bringing together the availability of genomic information and the intellectual pool in African countries to provide disease targeted training and research development. This has resulted in long term collaborations and access to diverse datasets from cohorts and genomes. Work we have performed included:
Sequencing and analysis of the tsetse fly genome,
Systems biology approaches to understanding the response of the host to infection with Leishmania
HIV diversity and evolution
Development of networks of laboratories for translation of genomic information.

Molecular profiling to understand disease
The fundamental research aspect of my work focuses on the development and deployment of systematic approaches to organizing molecular information. By systematic organization of molecular profiles, my group performs integration across biological processes leading to the discovery of key processes and targets involved in normal and diseased systems. Most molecular profiling exploits the availability of gene expression assays using arrays or next-generation sequencing. I take this information and transform it onto molecular pathways and networks of interaction. By performing this transformation in a highly systematic manner, I am able to generate consistent functional profiles of cells, tissues and populations. I have been applying this ‘pathway fingerprinting’ approach to the understanding of the key processes of disease development.
We have developed a novel means to determine the large scale interaction between pathways. By incorporating signatures generated from diseases, drug response, regulatory dynamics, genetic background and normal tissue-level expression, we generate a statistically robust framework that makes it possible to determine the relationship between drug pathway signatures, diseases, and normal and aberrant pathway activities within and between human samples, human transdifferentiated models, mouse and model organisms. This systems-level infrastructure for mechanisms of disease is directly linked to drug (intervention) activity. We term it PDx (pathway drug discovery) We are able to use PDx to repurpose existing drugs to address complex disease phenotypes
As part of our Cure Alzheimer’s CIRCUITS collaboration with Rudy Tanzi, Manolis Kellis and Rudolph Jaenisch, we are performing discovery and characterization of regulatory mutants that impact Alzheimer's disease progression, target prioritization, and discovery of potential drug interventions. Applying technologies such as these to incorporate ncRNA profiles within PDx as drug interventions is a logical next step.