Primary Investigator

Timothy Hla, Ph.D.

Patricia K. Donahoe Chair and Professor, Department of Surgery, Harvard Medical School

Investigator, Vascular Biology Program, Boston Children's Hospital

Tim Hla's laboratory has been investigating the role of lipid mediators, sphingosine 1-phosphate (S1P) and prostanoids in vascular biology and disease. In the 1990s, we cloned the inducible cyclooxygenase (COX-2) and the first S1P receptor. Our work defined how the COX-2 pathway regulated angiogenesis, cancer and inflammatory disease.

Recently, we are examining molecular mechanisms by which prostanoids interact with other lipid signaling systems to protect the vascular system and maintain health. Secondly, since our discovery of the S1P receptor we have been working on this novel signaling pathway to understand how it regulates vascular development and homeostasis and is dysregulated in vascular diseases. In addition, our work contributed to the development of S1P receptor inhibitors, which are being tested and used for treatment of a number of autoimmune diseases. Recently, we discovered that HDL-bound S1P activates vascular S1P receptors to inhibit vascular injury and disease. We also showed that proteins that bind to S1P, such as the HDL-bound apolipoprotein M (ApoM), direct specific biological functions of S1P by activating S1P receptors in unique ways. This mode of signaling, termed as, chaperone-dependent S1P signaling, may be a general mechanism for lipid mediators that are poorly soluble in water.

We are also examining novel mechanisms of S1P metabolism, export into the extracellular environment, capture and signaling by novel chaperones, receptor-dependent signaling mechanisms and cross-talk with other cytokine, growth factor signaling pathways. Such mechanistic information is useful not only to achieve a deeper understanding of vascular health and disease but also to develop new therapeutic entities based on the S1P signaling system, In fact, our laboratory is developing novel small molecular as well as protein biotherapeutics with the potential to modulate diseases such as heart disease, stroke, autoimmune diseases, eye disease and cancer.

About the Researcher

Timothy Hla received his Ph.D. in biochemistry from The George Washington University. Following a post-doctoral training period in which he worked in the lab of Thomas Maciag, he started his laboratory at the Holland Laboratory at the American Red Cross, Rockville, MD. He was recruited to the University of Connecticut School of Medicine in Farmington, CT where he founded the research Center for Vascular Biology and was eventually promoted to Professor. In 2009, he was recruited as a Professor and Director of the Center for Vascular Biology at Weill Cornell Medicine, Cornell University. He moved his research program to Boston Children's Hospital in 2016 where he is appointed as an investigator at the Vascular Biology Program and Patricia K. Donohoe Professor of Surgery at the Harvard Medical School.

Dr. Hla is an honorary member of the Japanese Biochemical Society, received an honorary M.D. degree from the Geothe University, Frankfurt, Germany and a MERIT award from the NHLBI, NIH in 2006.