The University of Texas Health Science Center at Houston
University of Texas MD Anderson Cancer Center
Department of Hematopoietic Biology and Malignancy
As a molecular biologist I have focused for the past 25 years on how nuclear events (transcription, epigenetics, recombination and hypermutation) drive development and transformation of B cells. To explore these questions my laboratory has engineered mouse models and applied genomics, CRISPR-screens, cryo-EM, single molecule tracking and bioinformatic tools. Some highlights of our research are the co-discovery of transcriptome amplification, a process whereby the transcription program of G0 lymphocytes is globally and proportionally amplified during activation. We have also helped resolve the long-standing question of why B cells are particularly prone to tumor development by unravelling the driving force behind antibody gene translocations. In 2010, I organized the NIH Regulome Project, a collaborative program between intramural and extramural investigators to explore mechanisms of transcription in normal and tumor cells. These efforts revealed that oncogenes expressed in most tissues (e.g., Myc, Pim1) often change their enhancer repertoire during ontogeny, leading to differential promoter function. Other discovered were how nuclear architecture modulates transcription and can drive the formation of chromosomal translocations in human cancers. More recently we solved the structure of the megadalton Mediator complex at atomic resolution. This advance has provided key insights into the regulation of PolI activity and opened new avenues of transcriptional research that our team and others in the field are actively pursuing. Another longstanding interest of our lab has been the development of mouse models to produce therapeutic antibodies. One example is the development of a mouse line that generates camelid antibodies (nanobodies). We have used these mice to isolate highly neutralizing nanobodies against SARS-CoV-2 and HIV-1. Ongoing efforts seek to develop nanobodies against tumor antigens and viral receptors.
Education & Training
PhD - Rockefeller University