Lora Talley Watts, Ph.D.Instructor Research
University of Texas Helath Science Center San Antonio, 2005
McDermont Building 2.706
Dr. Watts joined the Department of Cellular and Structural Biology as a postdoctoral fellow under the mentorship of James Lechleiter, Ph.D. and was promoted to Research Instructor in November of 2011. She is also an instructor for Dental Gross Anatomy. Dr. Watts is an active member of the research community on the campus of UTHSCSA and is currently the vice president for the Women's Faculty Association. In addition, Dr. Watts is active in the community, especially in providing mentorship and scientific outreach to neighborhood school children in hopes of instilling the value of scientific education to the youth of San Antonio. Dr. Watts is a member of the Society for Neuroscience and the American Heart Association. Dr. Watts has extensive experience in molecular and cellular techniques as well as in vivo imaging using confocal microscopy for determining neuroprotection following stroke and traumatic brain injury. More recently Dr. Watts has learned MRI technologies to further assess neuoprotection following a stroke.
Even with improvements in medical interventions, there are currently few neuroprotective agents clinically available that are capable of counteracting neuronal loss following stroke. Due to the severe neurological outcomes faced by stroke patients and the resulting financial impact on their families and society, I have focused my research on discovering novel treatment options for stroke. As a graduate student the focus of my research was the interaction of astrocytes and neurons in a model of Fetal Alcohol Syndrome, culminating in the novel finding that astrocytes provide neuroprotection from ethanol exposure through a glutathione mediated pathway. This project was supported by an Individual F31 NIH Predoctoral National Research Service Award (NIH-National Institute of Alcohol Abuse and Alcoholism) and the results were reported in the Journal of Neuroscience Research and the Journal of Neurochemistry.
This project facilitates my interest in the role of astrocytes within the brain as they comprise a significant portion of the brain but were deemed as mere mechanical supports for neurons for many decades. Over the last fifteen years the literature has exploded with data supporting a more active participation of astrocytes in brain function and pathology of disease. It is now well established that astrocytes play a fundamental role in signaling, maintenance and protection of the brain.
During my postdoctoral fellowship under James Lechleiter, Ph.D. I focused my research on the role of astrocyte physiology in a Rose Bengal induced-photothrombotic model (in vivo stroke model) to determine the neuroprotective roles of astrocytes following stroke. The data generated suggest that the neuroprotective ability of astrocytes diminishes with age. In addition, the purinergic receptor (P2Y-R) signaling pathway to boost astrocyte energy metabolism has resulted in significant increases in the resistance of astrocytes and neurons to oxidative stress. This stimulated protective mechanism decreases during aging, but remarkably, its magnitude in old astrocytes is comparable to stimulated young astrocytes. More recently, I propose to take the next logical steps to test this promising neuroprotective drug in a more clinically relevant model of stroke (embolic middle cerebral artery occlusion) in rats. Moreover, we will determine the efficacy of the combination therapy of 2meSADP and rt-PA treatment. Non-invasive, whole-brain MRI will be used to detect ischemic penumbra and longitudinally monitor treatment effects to optimize the treatment time window. Comparisons will be made with biochemical and behavioral measures.
My central hypothesis is that 2meSADP will reduce infarct size by maintaining energetics and extending survival to allow rt-PA to restore blood flow to the ischemic penumbra. This work will set the stage for further evaluation of other neuroprotective drugs and this approach is readily translatable to the clinical setting. This work was initially supported by an Institutional T32 Postdoctoral Fellowship through the National Institute of Aging and by and Individual F32 Postdoctoral National Merit Research Award (NIH-National Institute of Neurological Disorders and Stroke). This project builds on my prior work utilizing similar model systems (co-culture models, in vitro, ex vivo and in vivo models) as well as cellular, molecular and whole animal approaches to delineate novel treatment options for stroke patients. The success of the proposed study will provide novel targets for the development of neuroprotective treatments for patients that currently have limited treatment options.
Cell culture of neurons and astrocytes
Whole animal stroke methodologies (MCAO and Rose Bengal induced Photothrombosis)
Rathinam ML, Watts LT, Narasimhan M, Riar AK, Mahimainathan L, Henderson GI. (2012) Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat. Environ Toxicol Pharmacol. 2012 Mar;33(2):353-60.
Zheng W, Watts LT, Holstein DM, Prajapati SI, Keller C, Grass EH, Walter CA, Lechleiter JD. (2010) Purinergic receptor stimulation reduces cytotoxic edema and brain infarcts in mouse induced by photothrombosis by energizing glial mitochondria. PLoS One. 2010 Dec 22;5(12):e14401.
Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC. (2008) Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18976-81.
Rathinam ML, Watts LT, Stark AA, Mahimainathan L, Stewart J, Schenker S, Henderson GI. (2006) Astrocyte control of fetal cortical neuron glutathione homeostasis: up-regulation by ethanol. J Neurochem. 2006 Mar;96(5):1289-300.
Watts LT, Rathinam ML, Schenker S, Henderson GI. (2005) Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death. J Neurosci Res. 2005 Jun 1;80(5):655-66.