Research

Tumor Immunotherapy

Under the umbrella of the Human Immune Therapy Center, our laboratory seeks to gain a greater understanding of the interactions between the immune system and tumors.  We are particularly interested in how CD4+ “helper” T cells and dendritic cells (which are responsible for activating T lymphocytes) contribute to the immunological control of tumors.  Our studies are intended to help develop vaccines against tumors.

I.  High Blood Pressure (hypertension) and Blood Pressure Sensitivity to Salt

Our research team consists of the Principal Investigator, Dr. Robin A. Felder (Pathology), co-investigator Dr. Robert M. Carey (Endocrinology), and co-investigator Dr. Pedro A. Jose (Pediatrics, Georgetown University, Washington, D.C.) and over 50 M.D.s, Ph.D.s, students and technologists that are studying the interaction between two regulatory pathways (dopamine and the renin angiotensin system) with key roles in kidney function and blood pressure regulation.  Our current program project grant is focused on investigating how the kidney regulates sodium transport and blood pressure through shared and independent molecular, cellular, and physiological pathways.

II.   Medical Automation and Robotics

The Medical Automation Research Center focuses on developing new automation technologies that improve the efficiency, safety and relevance of medical care.

Mechanisms of Differentiation in Hematologic Cell Lineages

Our lab has maintained two major, extramurally-funded areas of investigation in the field of hematology.  The first consists of the regulatory pathways involved in programming the early stages of megakaryocytic differentiation.  The second consists of the mechanisms underlying erythropoietin resistance in certain types of anemias.  The common thread linking all of the research projects over the years has been the study of mechanisms underlying hematopoietic lineage commitment, in particular the divergence of the erythroid and megakaryocytic lineages from a common progenitor cell.

Since its discovery, gene fusions have been viewed as unique features of cancer and they all result from chromosomal translocation. Our recent findings have turned this dogma “on its head.” We have shown that the fusion products can be present in normal cells and they can be made through a mechanism that doesn’t require DNA translocation. Precursor mRNAs from separate genes can be joined by “trans-splicing” and the chimeric RNA can then be translated into fusion protein. The lab is now working on finding more examples of “trans-splicing.” For that, we are taking two approaches: 1. candidate gene approach which involves stem cell culture and differentiation 2. genome-wide search approach which relies on bioinformatics analysis and deep sequencing technology.

Second focus of the lab is related to some recent findings of Genome-Wide Association Studies (GWAS). People have used the technology to find single nucleotide polymorphisms (SNPs) associated with higher or lower risks of many phenotypes including prostate cancer, diabetes, inflammatory bowl disease, even body height. The problem is that the studies often identify a lot of SNPs with no significant relative risks. What’s more, the SNPs are often located outside of the coding region of any gene. The gene we are studying has several SNPs that have been demonstrated to give carriers high risk for type 2 diabetes and lower risk for prostate cancer. We have shown the risk allele for diabetes is associated with higher expression level of the gene and knocking out the gene in mice has a protective effect against type 2 diabetes. We are now working to characterize the metabolic phenotype of the knockout mice and evaluate them for the risks of prostate cancer

Pathogenesis of myotonic muscular dystrophy.
Skeletal and Cardiac Muscle Biology.
RNA metabolism.
Mouse models of human disease.
RNA toxicity as a new paradigm for disease pathogenesis.

Myeloid cells, including granulocytes and macrophages, play a crucial role in the body’s de­fense against infections. Abnormalities in their functions and maturation cause various diseases. At the Trinh laboratory, we employ experimental and computational approaches to understand how proteins and RNAs act at chromatin level to control activities of key genes involved in normal myeloid cell maturation, leukemia development, myeloid cell – cancer cell communication in the tumor microenvironment, as well as drug response. The aims are to identify actionable molecular targets and diagnostic biomarkers, and to develop innovative therapeutic strate­gies for diseases such as cancer. Learn more

Papillomaviruses are the most prevalent sexually transmitted disease and the leading infectious cause of cancer in the US, with a yearly economic impact of about $2.9 billion (2). Despite a prophylactic vaccine, lethal clinical disease will be a significant problem for many decades to come world-wide.  Alpha genus human papillomaviruses (HPVs) cause benign squamous epitheliomas in which the virus persists and replicates.  With HPV types termed “high-risk”, the initially benign papilloma may evolve over time and develop into a malignancy.  “Low-risk” HPV types very rarely progress to malignancy, but can cause serious, and even life-threatening medical complications due to the size, numbers, and locations of the benign papillomas.

I study the structure and biology of papillomavirus oncoproteins. We study papillomavirus oncoproteins from both human and animals to uncover their biological logic and the mechanism by which they transform cells and promote cancer. By comparing oncoproteins from diverse papillomaviruses, we have begun to understand how these oncoproteins physically interact with their cellular targets, and influence host cell signaling pathways.