Dr. Hong obtained his Ph.D. in Microbiology at the University of California, Davis. He then studied global genetic and epigenetic regulations in mouse embryonic stem cells at the Harvard Institute of Human Genetics during his post-doctoral fellowship. In 2001, he was recruited as an Instructor at the Cutaneous Biology Research Center, Massachusetts General Hospital, and Harvard Medical School. After 5 years, he joined the Department of Surgery, Keck School of Medicine in 2005. Dr. Hong is a Professor of Surgery and affiliated with Norris Comprehensive Cancer Center. He also serves as the Director of Translational and Basic Science Research of Surgery Department and supervises all basis and translational research in the department. His main research interest is to understand the molecular and cellular controls of tissue fluid homeostasis in health and disease, including cancer, vascular malformation, brain fluid outflow, inflammation, viral infection, and wound healing, and to translate the knowledge to benefit human health. Dr. Hong received numerous awards for his outstanding research accomplishments, including the Seungman Cha Young Scientist Award, the STOP CANCER Award, Margaret E. Early Medical Research Foundation Young Investigator Award, James H. Zumberge Innovation Research Award, Concern Foundation Young Scientist Award, American Heart Association Award, The Wright Foundation Young Investigator Award, The U.S. Department Of Defense Congressionally Directed Medical Research Programs Breast Cancer Idea Award, March Of Dime Birth Defect Foundation Scholar Award, and American Cancer Society Research Scholar Award. Dr. Hong has trained and mentored more than 80 students (high school, undergraduate, graduate, and medical school), post-doctoral fellows, surgical residents, visiting scholars, and junior faculty members during the past 15 years at the Keck School of Medicine.
The research interests in the Hong laboratory are listed below.
1. Lymphatic Development and Differentiation
Although Hippocrates simultaneously discovered the blood and lymphatic system, the lymphatic system has been extremely understudied despite its vital role in human health and diseases, compared to the blood vascular system. About 100 years ago, Sabin proposed that lymphatics are generated from the blood vascular system. This Sabin’s theory has recently been confirmed using newly discovered molecular and cellular markers and research tools. We are interested in how various signal pathways control lymphatic development and differentiation. A better understanding of lymphatic development and differentiation will significantly help to treat many human diseases related to the lymphatic system.
We have recently launched an Organ-On-Chips program. Collaborating with other biomedical engineer groups, we aim to grow blood and lymphatic vessels on a chip to investigate the mechanisms of physiological and pathological angiogenesis and lymphangiogenesis. This new technology is powerful as it enables us to study the biology of vascular development and differentiation and models our organs and tissues for many biomedical and therapeutic purposes.
3. Development of Lymphedema Therapy
Surgery-related lymphedema is the leading morbidity that is associated with breast cancer survivors. To date, non-invasive therapeutic approaches are unavailable for this disfiguring, painful and demoralizing illness. We have recently published the therapeutic efficacy of retinoic acid against surgery-associated lymphedema in the prestigious journal Circulation. Our study found that retinoic acid could regenerate damaged lymphatic system and prevent potential lymphedema using animal models. We aim further to confirm this new therapy in rats and large animals and eventually bring it to clinical trials. Because retinoic acids have been extensively studied for their medicinal properties and are already used in clinics for other diseases, the new approach presents great promise and hope to patients suffering from surgery-associated lymphedema.
4. Fluid Homeostasis and Outflow Facility in the Eye
The lymphatics play essential roles in tissue fluid homeostasis in the interstitial space. Similarly, Schlemm’s canal (SC), a specialized vascular structure in the eye, controls the fluid homeostasis of the eye's anterior chamber. SC is an endothelium-lined channel that encircles the margin of the cornea and drains the aqueous humor from the anterior chamber of the eye into the circulation through collector channels. As the intraocular pressure (IOP) is closely correlated with the aqueous humor outflow (AHO), SC plays a key role in regulating IOP in the eye. When the draining function of SC becomes compromised, the IOP could be dramatically elevated and damage the ocular nerve, possibly causing glaucoma. Directly connected to the aqueous vein, SC has long been thought to be a venous extension, whose inner wall is lined by blood vascular endothelial cells (BECs). Interestingly, SC has also been known to display molecular, structure, and functional features of lymphatic vessels, which are responsible for draining the interstitial fluids into the circulation. During development, lymphatic endothelial cells (LECs) are differentiated from BECs and this BEC-to-LEC fate reprogramming process is exquisitely controlled by a homeodomain transcription factor Prox1. Recently, my group, together with a vascular biology group in Korea, has published an exciting study, demonstrating that lymphatic regulator PROX1 determines SC integrity and identity. In addition, we have collaborated with other groups in two other studies on SC's development and maintenance. We are thrilled to utilize our expertise to understand better how fluid homeostasis and intraocular pressure are controlled in healthy and glaucoma eyes. We are interested in defining the molecular mechanism by which fluid flow directs the development and maintenance of SC through the shear stress regulator, Klf4. Our experience and resource would contribute to advancing the knowledge of the molecular controls of intraocular pressure with therapeutic implications for glaucoma.
5. Stem Cell Research
We study the molecular mechanism underlying the vascular differentiation of embryonic stem (ES) and adipose-derived stem cells (ADSC) with three goals. (a) to acquire a better understanding of the embryonic and postnatal genetic program that specifies vascular and lymphatic endothelial cells, (b) to develop technology that allows maximal differentiation efficiency for 3-D printing of organs, and (c) to acquire the clinical-grade vascular building blocks to treat vascular diseases, including vascular malformation and lymphedema.
6. Cancer Development and Metastasis
The majority of cancers recruit and invade lymphatic vessels for their metastasis. We are interested in how breast and colon cancers interact with lymphatic vessels to promote their metastasis. Our preliminary data suggest that tumor-induced tissue pressure could play a previously unidentified role in their spread. Separately, various pathogens, such as Kaposi sarcoma herpes virus (KSHV), directly infect vascular endothelial cells and cause neoplasm in HIV- and organ transplant patients. We are studying the molecular and cellular interactions between the host and the pathogens.