Faculty Biography

Shibani Pati, M.D., Ph.D.

Current Areas of Research

I am a vascular biologist with an interest in the role of vascular compromise in the pathogenesis of human disease. My specific areas of investigation involve the use of stem cells and novel resuscitative modalities that can mitigate endothelial injury. Abnormalities in vascular permeability leading to inflammation, tissue edema, and end-organ dysfunction significantly contribute to the morbidity and mortality associated with a number of human disease processes. For example, although a number of factors contribute to the high mortality and morbidity associated with traumatic brain injury (TBI), the development of cerebral edema with brain swelling remains one of the most significant predictors of outcome. Similarly both hemorrhagic shock and septic shock are characterized by abnormal vascular permeability, which contributes to the development of shock-associated acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite the clear importance of abnormal vascular permeability in a number of human disease processes, there exists no therapeutic modality in current use to treat it. Mechanistically, my laboratory has compelling data demonstrating that the positive effects of infused MSCs in preventing pathologic vascular edema (in TBI and acute lung injury models) relate to secreted factors acting in a paracrine fashion upon contact with the vascular endothelium. Building upon these findings we have probed deeper to identify candidate factors that mediate the vascular stabilizing effects of MSCs. Preliminary data suggests that such factors dosed at a physiologically relevant concentrations can largely recapitulate the beneficial effects of MSCs on vascular permeability.
In the area of endothelial injury, we have begun to investigate the effect of various resuscitation fluids on endothelial injury and function in trauma. The goal of this project is two-fold- 1) to understand how hemorrhage affects the endothelium and 2) to optimize modalities of resuscitation to improve patient care in both civilian and military settings. In addition, my laboratory is currently working to develop markers of vascular instability in cell models to be used to screen small molecule libraries for novel agents for treatment of diseases characterized by vascular injury.
The ultimate goal of my complete research effort is to translate from "bench to bedside" therapeutic interventions that can be used to mitigate vascular injury and help disease outcome in patients

EDUCATION

Degree-Granting Education
Princeton University, Princeton, NJ, A.B., 1992, Molecular Biology

University of Maryland Baltimore, MD, M.D. 1998, Medicine

University of Maryland Baltimore, MD, Ph.D. 2001 Microbiology and Immunology

Postgraduate Training
1.Postodoctoral Fellowship, University of Maryland , Baltimore, MD, Institute of Human Virology Dr. Robert Gallo's Laboratory 2002-2005.

2. Vivian Smith Postdoctoral Fellowship in Neuroscience Baylor College of Medicine and
University of Texas Houston, Texas Dr. Pramod Dash's Laboratory 2006-2008

Selected Publications

1.Pati S*., Rogers, T, Khakoo, AY, Lederer, J.Mesenchymal Stem Cells Stimulate Protective Genetic Programming of Injured Cardiac Ventricular Myocytes" Journal of Mol. And Cell. Cardiology 2010 * Indicates Co-First with Rogers, T.

2.Pati S, Khakoo AY, Zhao J, Jimenez F, Gerber M, Harting MT, Redell JB, Grill RJ, Matsuo Y, Guha S, Cox CS, Reitz MS, Holcomb JB, Dash PK. Human mesenchymal stem cells inhibit vascular permeability by modulating VE-cadherin/beta-catenin signaling. Stem Cells Dev. 2010 May 6. [Epub ahead of print]PMID: 20446815

3.Pati S, Matijevic N, Doursout MF, Ko T, Cao Y, Deng X, Kozar RA, Hartwell E, Conyers J, Holcomb JB. Protective effects of fresh frozen plasma on vascular endothelial permeability, coagulation, and resuscitation after hemorrhagic shock are time dependent and diminish between days 0 and 5 after thaw.J of Trauma. 2010 Jul;69 Suppl 1:S55-63.PMID: 20622621

4.Walker PA, Shah SK, Jimenez F, Gerber MH, Xue H, Cutrone R, Hamilton JA, Mays RW, Deans R, Pati S, Dash PK, Cox CS Jr Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: Preserving the blood brain barrier via an interaction with splenocytes. Exp Neurol. 2010 Jul 15. PMID: 20637752

5. Dash PK, Orsi SA, Zhang M, Grill RJ, Pati S, Zhao J, Moore AN. Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats.
PLoS One. 2010 Jun 30;5(6):e11383.PMID: 20614021

6.Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress.Chintalgattu V, Ai D, Langley RR, Zhang J, Bankson JA, Shih TL, Reddy AK, Coombes KR, Daher IN, Pati S, Patel SS, Pocius JS, Taffet GE, Buja LM, Entman ML, Khakoo AY.
J Clin Invest. 2010 Feb 1;120(2):472-84. doi: 10.1172/JCI39434. Epub 2010 Jan 11.PMID: 20071776

7.Letourneau PA, Pati S, Gerber MH, Jimenez F, Holcomb JB.
Fresh Frozen Plasma Increases Adhesion Molecule Expression on Human Pulmonary Endothelial Cells. J Surg Res. 2010 May 20. [Epub ahead of print]PMID: 20599210

8. Pati, S., Sara Orsi, B.S.; Pramod Dash, Ph.D. Intra-hippocampal administration of the VEGF receptor blocker PTK787/ZK222584 Impairs lon-term memory. Brain Res. 2008 Dec 7.

9.Harting M., Jiminez F., Pati S., Baumgartner J., and Cox C. Immunophenotype characterization of rat mesenchymal stem cells, Cytotherapy

10. Pati S.*, Khakoo AY., Anderson SA., Reid W., Elshal MF., Rovira II, Nguyen AT., Malide D., Combs CA., Hall G., Zhang J., Raffeld M., Rogers TB., Stetler-Stevenson W., Franks JA., Reitz M., Finkel T. Human Mesenchymal Stem Cells exert potent antitumorigenic effects in a model of Kaposi's Sarcoma. J. Exp. Med. 2006 May 15;203(5):1235-47. * Indicates Co-first with A. Khakoo

Location & Contact

6431 Fannin Street
MSB 4.020
Houston, Texas 77030
Tel: 713-500-7200
Fax: 713-500-7213

Contact Information

• Shibani Pati, MD, PhD

• Assistant Professor - Research
  Division of Acute Care Surgery, Department of Surgery,
  The University of Texas Medical School at Houston

• Department of Surgery

• 6431 Fannin Street
  MSB 5.212
  Houston, Texas 77030

• phone: (713) 500-7346
  e-mail: Shibani.Pati
  @uth.tmc.edu