Drug Discovery, Enzymology, Imaging, Ion Channels, Membrane Biology, Neurobiology, Protein Dynamics, Signal Transduction
The mechanisms and treatment of epileptogenesis in adult onset epilepsy and the overlap between epileptic encephalopathy and Alzheimers disease.
My lab currently investigates mechanisms of both acquired and congenital adult onset epilepsy with both translational clinical studies and basic science. Caspase-3 has increased expression in epileptogenic tissue and is a potential target for pharmacologic intervention to limit epileptogensis and seizures. Caspase-3 has been shown to modulate amyloid precursor protein processing and amyloid protein is also highly expressed in the brain tissue of patients with epilepsy. Investigation into the overlaps between epileptic encephalopathy and Alzheimer’s disease may yield novel mechanisms and treatments for both conditions. As a non-lethal role for caspase-3 becomes better appreciated it may mean that activation of Caspase-3 may be a powerful novel mechanism to prevent seizures. It’s high level of expression in both epileptic and Alzheimer’s brain tissue may reflect a defense mechanism rather then a pathology of the condition.
As amyloid is known to require action potential activity for processing from precursor to amyloid beta and alpha, it is hypothesized that amyloid concentration in the cerebral spinal fluid could be used as a biomarker of seizure. Currently in medicine there are no biomarkers for seizure activity with a high enough sensitivity and specificity to be clinically dependable. As well, it may be the concentrations of the APP products are markers for epileptogenesis, with different ratios in a first time seizure compared to years of seizures. We are analyzing tissue samples from patients to address these questions.
Another are of interest in the lab is in honing identification of seizure onset zones in patients with epilepsy who are potential surgical resection candidates. The most common surgical resection is temporal done for mesial temporal sclerosis (MTS). As MTS progresses it erodes a patient’s capacity for short term memory, a function that does not recover even with a successful surgery. Identifying patients early, before significant damage has been done by the seizures, for curative surgery is a goal of the epilepsy treatment community. Early curative surgery improves patient’s lives, ability to work, drive and have meaningful home lives. Current techniques are dependent on identifying the seizure onset zone only after significant pathology and injury have occurred. We are using a novel imaging technique, magnetic resonance elastography (MRE) along with neuro-psychological tasks to see if this new technique can identify the area of deficit earlier.
B.S. 1993 University of Oregon
Ph.D. 2005 University of Illinois Urbana-Champaign, Neuroscience Program
M.D. 2007 University of Illinois College of medicine, Medical Scholars MD/PhD program at UIUC 1996 – 2005
Residency 2008 -2011 Neurology Residency, Partners Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, Harvard Medical School
Fellowship 2011-2013 Epilepsy Fellowship, Massachusetts General Hospital, Harvard Medical School
Postdoc. 2010-2013 Postdoctoral research on caspase-3 regulation. Laboratory of Dr. Rudolph Tanzi. MIND institute, Department of Neurology, Massachusetts General Hospital/ Harvard Medical School
Additional Campus Affiliations
Research Assistant Professor, Clinical Sciences
Research Assistant Professor, Beckman Institute for Advanced Science and Technology
Walters, J. M., Kim, E. C., Zhang, J., Jeong, H. G., Bajaj, A., Baculis, B. C., Tracy, G. C., Ibrahim, B., Christian-Hinman, C. A., Llano, D. A., Huesmann, GR., & Chung, H. J. (2022). Pharmacological inhibition of STriatal-Enriched protein tyrosine Phosphatase by TC-2153 reduces hippocampal excitability and seizure propensity. Epilepsia, 63(5), 1211-1224. https://doi.org/10.1111/epi.17192
Wechsler, R. T., Wheless, J., Zafar, M., Huesmann, G. R., Lancman, M., Segal, E., Chez, M., Aboumatar, S., Patten, A., Salah, A., & Malhotra, M. (2022). PROVE: Retrospective, non-interventional, Phase IV study of perampanel in real-world clinical care of patients with epilepsy. Epilepsia Open, 7(2), 293-305. https://doi.org/10.1002/epi4.12575
Hiscox, L. V., McGarry, M. D. J., Schwarb, H., Van Houten, E. E. W., Pohlig, R. T., Roberts, N., Huesmann, G. R., Burzynska, A. Z., Sutton, B. P., Hillman, C. H., Kramer, A. F., Cohen, N. J., Barbey, A. K., Paulsen, K. D., & Johnson, C. L. (2020). Standard-space atlas of the viscoelastic properties of the human brain. Human Brain Mapping, 41(18), 5282-5300. https://doi.org/10.1002/hbm.25192
Huesmann, G. R., Schwarb, H., Smith, D. R., Pohlig, R. T., Anderson, A. T., McGarry, M. D. J., Paulsen, K. D., Wszalek, T. M., Sutton, B. P., & Johnson, C. L. (2020). Hippocampal stiffness in mesial temporal lobe epilepsy measured with MR elastography: Preliminary comparison with healthy participants. NeuroImage: Clinical, 27, . https://doi.org/10.1016/j.nicl.2020.102313
Gupta, D. K., Huesmann, G. R., & Huesmann, L. R. (2018). Is terrorism the result of root causes such as poverty and exclusion? In Contemporary Debates on Terrorism, 2nd Edition (pp. 149-163). Taylor and Francis.