Brian Herman, Ph.D., Professor
University of Connecticut Medical School
1980

(210) 567-3800
HERMANB@UTHSCSA.EDU

Dr. Herman assumed the position of Professor & Chair of the Department of Cellular & Structural Biology at the UTHSCSA in June 1998, serving in this capacity until October 2004, when he assumed the position of Vice President for Research at the UTHSCSA. Dr. Herman is a past recipient of an American Cancer Society Faculty Research Award, (1991-1995), the Dozer Fellowship from Ben Gurion University, Israel, (1998) and an NIH (National Institute of Aging) Method to Extend Research in Time (MERIT) Award (1994-2004). In 2004, Dr. Herman received the UTHSCSA Presidential Distinguished Scholar Award. In 2005, he received a second NIH (National Institute of Aging) Method to Extend Research in Time (MERIT) Award (2005-2015). He is listed in American Men and Women of Science, is an Editor of the Journal Microscopy & Microanalysis, an Associate Editor of the Journal of Cellular Biochemistry and currently serves on the Editorial Boards of BioTechniques, Journal of Biomedical Optics, American Journal of Physiology: Cell Physiology, Mechanisms of Aging and Development and the Journal of Biological Chemistry. Dr. Herman has served on multiple NIH and NSF study sections including a four-year term on the NIH Cell, Development and Function-2 study section, two of which he served as Chair of the study section. Dr. Herman serves as faculty in Medical Histology, Graduate Cell Biology and in UTHSCSA course in Optical Microscopy for the Biological Sciences.

Research Interests - Despite increasing interest in the relationship of aging and apoptosis in recent years, a role for apoptosis in aging remains obscure. Enhanced levels of apoptosis during aging could benefit the organism by serving as a self-protective mechanism to remove increased numbers of dysfunctional cells as a result of aging and then replacing lost cells by normal proliferation in order to maintain homeostasis (i.e. in liver). Conversely, enhanced levels of apoptosis during aging could be detrimental to the organism by causing excessive cell death and the decline of organ function attendant with aging especially in post-mitotic tissues such as the brain.

The mitochondrial theory of aging proposes that oxidative damage, and in particular oxidative damage to mitochondria, is an important causal factor in the aging process. Aging is associated with lowered anti-oxidant defense mechanisms and increased oxidative damage to mitochondria. The mitochondria are central to the apoptotic process as a source and a target of ROS and as the site of initiation of apoptosis. This coupled with the fact that oxidative damage to mitochondrial proteins, lipids and DNA increases with age, suggests that age-dependent oxidative-induced alterations in mitochondrial function and their attendant effects on apoptosis, may play a role in the regulation of the aging process.

We have recently found an age-dependent increase in the endogenous activity of caspases that are known to be responsible for the execution of apoptosis in rat liver, lung and spleen. Our studies also identified caspase-2 as the first caspase that was seen to increase during aging and inhibition of caspase-2 reversed the age-dependent increase in sensitivity of hepatocytes to oxidative stress. We have also shown that caspase-2 is localized in mitochondria and is activated by oxidative stress, fibroblasts isolated from mice lacking caspase-2 are selectively resistant to mitochondrial oxidant stress-induced apoptosis and that old male mice lacking caspase-2 have severe age-dependent osteoporosis compared to age-matched male wild type mice. These data suggest that caspase-2 is a putative effector of mitochondrial oxidant stress-induced apoptosis and that this caspase may regulate alterations in apoptotic activity that impact aging (lifespan). In particular, old male caspase-2 null mice also had increased bone turnover rate, which is characteristic of osteoporotic patients. In addition, caspase-2 deficiency resulted in increased numbers of osteoclasts, the cell type responsible for bone resorption, but had no effect on the number of osteoblasts, the cell type responsible for bone formation. Thus, our findings suggest that caspase-2 may play an important role in the onset of age-dependent osteoporosis. Our current areas of research focus are examining the hypotheses that caspase-2 modulates mitochondrial oxidative stress-induced apoptosis in hepatocytes and neurons and such apoptosis affects aging in a tissue specific fashion. We are also testing the theory that loss of oxidative stress-induced caspase-2 mediated apoptosis results in an accelerated age-related accumulation of oxidative damage, leading to alterations in bone turnover during aging.

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PUBLICATIONS:
Zhang, Y. and Herman, B. 2006. ARC protects rat cardiomyocytes against oxidative stress through inhibition of caspase2 mediated mitochondrial pathway. J. Cellular Biochemistry. Apr 25; 99(2):575-588.

Ramanujan, V.K., Biener, G., and Herman, B. 2006. Scaling Behavior in Mitochondrial Redox Fluctuations. Biophysical Journal. May 15; Vol. 90:(10)L70-2. Epub Mar 24.

Biener, E., Charlier, M., Ramanujan, V.K., Daniel, N. Eisenberg, A., Bjorbaek, C., Herman, B., Gertler, A., and Djiane, J. 2005. Quantitative FRET imaging of leptin receptor oligomerization kinetics in single cells. Biol Cell. Dec;97(12):905-19.

Ramanujan, V.K., Zhang, J-H., Biener, E., and Herman, B. 2005. Multiphoton Fluorescence Lifetime Contrast in Deep Tissue Imaging: Prospects in Redox Imaging and Disease Diagnosis. J. Biomed Optics. Sep-Oct;10(5):051407.

Ran Q., Liang H, Gu M, Qi W, Walter CA, Roberts LJ 2nd, Herman B, Richardson A, Van Remmen H. 2004. Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J Biol Chem. Dec 31;279(53):55137-46.