R. Sathish Srinivasan, Ph.D.
Cardiovascular Biology Research Program
Oklahoma Medical Research Foundation
Oklahoma City, OK
In healthy adult humans, the lymphatic vasculature collects almost 12 liters of lymph/day. Mutations in genes that regulate lymphatic vascular development lead to lymphedema, the accumulation of interstitial fluid in tissues. The health consequences of lymphedema include pain, obesity, fibrosis, high blood pressure, and even angiosarcoma. Millions of people suffer with lymphedema in the United States alone. However, there are currently no treatments for lymphedema. Barriers to advancing new therapies include a poor understanding of lymphatic functional anatomy and a lack of technologies for repairing damaged structures. The goal of the Srinivasan lab is to identify the molecular mechanisms underlying the development of lymphatic structures in order to facilitate the generation of the tools required to repair lymphatic defects.
Srinivasan RS, Dillard ME, Lagutin OV, Lin F-J, Tsai S, Tsai M-J, Samokhvalov, Oliver G. Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes Dev. (cover image) 2007 Oct 1;21(19):2422-32.
Srinivasan RS, Geng X, Yang Y, Wang Y, Mukatira S, Studer M, Porto MP, Lagutin O, Oliver G. The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. Genes Dev. 24:696-707, 2010.
Srinivasan RS, Oliver G. Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes Dev. 25:2187-2197, 2011.
Srinivasan RS, Escobedo N, Yang Y, Interiano A, Dillard ME, Finkelstein D, Mukatira S, Gil HJ, Nurmi H, Alitalo K, Oliver G. The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors. Genes Dev. 2014 Oct 1;28(19):2175-87. 5.
Geng X, Cha B, Mahamud MR, Lim KC, Silasi-Mansat R, Uddin MK, Miura N, Xia L, Simon AM, Engel JD, Chen H, Lupu F, Srinivasan RS. Multiple mouse models of primary lymphedema exhibit distinct defects in lymphovenous valve development. Dev Biol. (cover image) 2016 Jan 1;409(1):218-33.
Cha B, Geng X, Mahamud R, Fu J, Mukherjee A, Kim Y, Jho E-h, Kim TH, Kahn ML, Xia L, Dixon JB, Chen H, Srinivasan RS. Mechanotransduction activates Canonical Wnt/-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves (Genes Dev, in press).
R. Sathish Srinivasan (PI): Sathish did his postdoctoral training in the lab of Dr. Guillermo Oliver at St. Jude Children’s Research hospital, Memphis. Sathish demonstrated the venous contribution to lymphatics, identified the role of the transcription factor Coup-TFII in the specification of lymphatic endothelial cells, characterized the lymphovenous valves (LVVs) and demonstrated the existence of a feedback loop between the transcription factor Prox1 and the signaling molecule Vegfr3. While not driving people crazy at work, Sathish takes his daughters to the zoo, while all the time imagining the lymphatic vessels of the various animals (beware zoo keepers). At home Sathish kills a lot of plants in the name of gardening, unsuccessfully attempts to beat his 6-year old daughter in chess, watches Samurai movies, and dreams about a day when he can get back to his Karate training.
Xin Geng (Staff Scientist): Xin is a developmental biologist and the technical wizard of the lab. She established the protocol for the analysis of LVVs by SEM, and she is the first author of our lab’s first publication that demonstrated the close correlation between defective LVVs and primary lymphedema. When not working, Xin participates in Zumba or body pump class, tries out new Chinese recipes, and takes care of the two daughters that she has with Sathish.
Boksik Cha (Postdoctoral fellow): Boksik is the Biochemistry maestro of the lab and discovered the relationship between canonical Wnt signaling, mechanical stimuli, and lymphatic vascular development (Genes Dev, in press). When not working in the lab, Boksik takes care of a 2 month-old baby so his wife and daughter (8) can go shopping at TJ Maxx, listens to 90s pop music that no one else could recognize and dreams about the day when he can go snow boarding in the Rockies.
Riaj Mahamud (graduate student): As the baby of the lab, Riaj spends a lot of time improving his technical skills. When not getting inspirational advice from Sathish, Riaj watches movies on the internet, listens to Bengali music, and dreams about his upcoming wedding (not realizing what he is getting into).
Lijuan Chen (Research Assistant): A master of many trades, Lijuan breeds, tails, genotypes and weans thousands of mice with organizational sleight of hand. While not taking care of mice, Lijuan drives Sathish crazy by demanding more work. While not at work, Lijuan spends her time in keeping her house impeccably clean and her teenage daughter in check.
Anita James (Administrative Assistant): As den mother of the Srinivasan lab, Anita babysits Sathish by taking care of loads of paperwork that the PI despises, provides wise counsel to the “cubs” in the lab, and acts as administrator for all things grant related. When not working, Anita spends time volunteering in her church and in the community, and can often be found yelling loudly at the television when an OKC Thunder basketball game is on.
Inside OMRF: Lijun Xia, Courtney Griffin, Florea Lupu, Lorin Olson, Jasim Ahamed, Rod McEver.
Outside OMRF: Michael Davis (University of Missouri, Columbia), Hong Chen (Boston Children’s Hospital), J. Brandon Dixon (Georgia Tech), Joshua Scallan (University of South Florida), Tae Hoon Kim (University of Texas at Dallas), Douglas Engel (University of Michigan), Alex Simon (University of Arizona), Mark Kahn (University of Pennsylvania), Gwen Randolph (Washington University) and many other wonderful people.
GRC on Lymphatics (Ventura)
Developmental Vascular Biology and Genetics Workshop at Vascular Biology2014 (NAVBO, Pacific Grove, CA)
Laboratory Motto: It ain't over til it's over!