Rodney E. Kellems, PhD

Biography

Dr. Kellems received the PhD degree in 1974 from Princeton University for research that provided fundamental insight into mechanisms of protein import into mitochondria.   His graduate research it continues to be cited on a regular basis nearly 50 years after initial publication.  Postdoctoral research at Stanford University employed emerging techniques in molecular genetics to discover gene amplification as a novel mechanism of drug resistance in mammalian cells. These groundbreaking discoveries had major impact in cancer biology and laid the foundation for the discovery of amplified proto-oncogenes in cancer cells.  Gene amplification also had major practical impact in biotechnology where the process is the most frequently used method to overproduce proteins of medical importance in mammalian cells.

In 1978, Dr. Kellems accepted a faculty position at Baylor College of Medicine, where he developed a patented gene amplification technology that was licensed by Baxter Healthcare to produce large amounts of Factors VIII and IX to treat hemophilia.  While at Baylor he initiated a new research program to understand the metabolic and molecular basis for the severe combined immune deficiency (SCID) in humans that results from a deficiency in the enzyme adenosine deaminase (ADA).  For this purpose, his lab successfully devised a novel two-stage genetic engineering strategy to construct a mouse model of ADA-deficiency.  In 1997 Dr. Kellems moved to McGovern Medical School to Chair the Department of Biochemistry and Molecular Biology.   While at McGovern Medical School his lab continued research on ADA-deficiency and showed that, in addition to the expected SCID phenotype, the mice displayed numerous other phenotypes resulting from their enzyme deficiency. His lab and others have successfully used these mice as a discovery platform to determine the detrimental role of chronic excessive adenosine signaling in other disease conditions, including lung fibrosis,  priapism, pain, hearing loss, renal disease, and wound healing. Additionally, in collaboration with others, ADA-deficient mice were used in pre-clinical tests to show that gene replacement therapy could be successfully used to treat ADA-deficiency.   The clinical trials with ADA-deficient children that followed were among the first, and remain the best, examples of successful gene therapy to treat a human genetic disorder.

For the past fifteen years Dr. Kellems has collaborated with Professor Yang Xia to study the role of pathogenic autoantibodies in preeclampsia, a serious hypertensive condition of pregnancy. They showed that women with preeclampsia harbor autoantibodies that activate the major angiotensin receptor and that these autoantibodies cause preeclampsia when injected into pregnant mice.  Their research experience prompted them to formulate a working hypothesis that many forms of hypertension result from receptor activating autoantibodies, a condition they termed autoimmune hypertension.   Their research shows that the production of these autoantibodies is induced by inflammatory cytokines in a process that requires, transglutaminase-2 (TG2), a ubiquitous enzyme that catalyzes the posttranslational modification of glutamine residues on proteins.  These studies have revealed the essential role of TG2 in inflammation, autoimmunity and hypertension.

Dr. Kellems has received over 35 years of support from the National Institutes of Health, co-authored more than 160 papers and has been awarded three U.S. patents.  His published work has been cited more than 13,000 times.