Shibani Pati, MD, PhD

Professor In Residence
Laboratory Medicine
+1 415 502-1634

I am a translational vascular biologist with an interest in the role of endothelial dysfunction and vascular compromise in the pathogenesis of human disease. My specific areas of investigation involve the use of stem cell therapies and novel resuscitative modalities that can mitigate endothelial dysfunction and improve outcomes in traumatic injury. Areas of focus in the lab include traumatic brain injury (TBI), and hemorrhagic shock induced organ failure.

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 attenuate it. Our lab's focus is to understand the mechanisms of action that lead to organ failure in traumatic injury and to also discover novel therapies that improve outcomes. We are and have been part of number of pre-clinical and clinical trials investigating the therapeutic potential of stem cells, stem cell derived factors and novel blood products. This has led to exciting new avenues for the discovery of novel therapeutic agents that mitigate vascular injury.

Publications: 

Histone deacetylase-6 modulates the effects of 4°C platelets on vascular endothelial permeability.

Blood advances

Miyazawa B, Trivedi A, Vivona L, Lin M, Potter D, Nair A, Barry M, Cap AP, Pati S

RECOVERY OF ENDOTHELIOPATHY AT 24 HOURS IN AN ESTABLISHED MOUSE MODEL OF HEMORRHAGIC SHOCK AND TRAUMA.

Shock (Augusta, Ga.)

Barry M, Trivedi A, Vivona LR, Chui J, Pathipati P, Miyazawa B, Pati S

Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock.

The journal of trauma and acute care surgery

Zeineddin A, Wu F, Chao W, Zou L, Vesselinov R, Chipman AM, Dong JF, Huang H, Pati S, Kozar RA

Lyophilized plasma resuscitation downregulates inflammatory gene expression in a mouse model of sepsis.

The journal of trauma and acute care surgery

Barry M, Wu F, Pati S, Chipman A, Geng H, Kozar R

FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock.

The journal of trauma and acute care surgery

Dixon A, Beiling M, Smith S, Behrens B, Appleman L, Rick E, Murphy J, Madtson B, McCully B, Goodman A, Kanlerd A, Schaller T, Subramanian S, Trivedi A, Pati S, Schreiber M

Mesenchymal Stem Cell Extracellular Vesicles Mitigate Vascular Permeability and Injury in the Small Intestine and Lung in a Mouse Model of Hemorrhagic Shock and Trauma.

The journal of trauma and acute care surgery

Barry M, Trivedi A, Pathipati P, Miyazawa BY, Vivona LR, Togarrati PP, Khakoo M, Tanner H, Norris P, Pati S

Treating the endotheliopathy of SARS-CoV-2 infection with plasma: Lessons learned from optimized trauma resuscitation with blood products.

Transfusion

Pati S, Fennern E, Holcomb JB, Barry M, Trivedi A, Cap AP, Martin MJ, Wade C, Kozar R, Cardenas JC, Rappold JF, Spiegel R, Schreiber MA

Cryoprecipitate Attenuates the Endotheliopathy of Trauma in Mice Subjected to Hemorrhagic Shock and Trauma.

The journal of trauma and acute care surgery

Barry M, Trivedi A, Miyazawa BY, Vivona LR, Khakoo M, Zhang H, Pathipati P, Bagri A, Gatmaitan MG, Kozar R, Stein D, Pati S

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials.

Annals of surgery

Holcomb JB, Moore EE, Sperry JL, Jansen JO, Schreiber MA, Del Junco DJ, Spinella PC, Sauaia A, Brohi K, Bulger EM, Cap AP, Hess JR, Jenkins D, Lewis RJ, Neal MD, Newgard C, Pati S, Pusateri AE, Rizoli S, Russell RT, Shackelford SA, Stein DM, Steiner ME, Wang H, Ward KR, Young P

Freeze-dried platelets promote clot formation, attenuate endothelial cell permeability, and decrease pulmonary vascular leak in a murine model of hemorrhagic shock.

The journal of trauma and acute care surgery

Trivedi A, Potter DR, Miyazawa BY, Lin M, Vivona LR, Khakoo MA, Antebi B, Lee A, Ishler B, Dickerson M, Kozar R, Schreiber MA, Holcomb JB, Fitzpatrick GM, Pati S

The effects of human prothrombin complex concentrate on hemorrhagic shock-induced lung injury in rats: Implications for testing human blood products in rodents.

The journal of trauma and acute care surgery

Potter DR, Trivedi A, Lin M, Miyazawa BY, Vivona LR, McCully B, Nair A, Schreiber MA, Pati S

Fresh frozen plasma attenuates lung injury in a novel model of prolonged hypotensive resuscitation.

The journal of trauma and acute care surgery

Chipman AM, Wu F, Pati S, Burdette AJ, Glaser JJ, Kozar RA

Resuscitative Strategies to Modulate the Endotheliopathy of Trauma: From Cell to Patient.

Shock (Augusta, Ga.)

Wu F, Chipman A, Pati S, Miyasawa B, Corash L, Kozar RA

Aggressive treatment of acute kidney injury and hyperkalemia improves survival in a combat relevant trauma model in swine.

American journal of surgery

Smith S, Behrens B, McCully B, Murphy J, Bommiasamy A, Goodman A, Dewey E, Pati S, Schreiber M

Is all plasma created equal? A pilot study of the effect of interdonor variability.

The journal of trauma and acute care surgery

Chipman AM, Pati S, Potter D, Wu F, Lin M, Kozar RA

Platelet-derived- Extracellular Vesicles Promote Hemostasis and Prevent the Development of Hemorrhagic Shock.

Scientific reports

Lopez E, Srivastava AK, Burchfield J, Wang YW, Cardenas JC, Togarrati PP, Miyazawa B, Gonzalez E, Holcomb JB, Pati S, Wade CE

Regulation of endothelial cell permeability by platelet-derived extracellular vesicles.

The journal of trauma and acute care surgery

Miyazawa B, Trivedi A, Togarrati PP, Potter D, Baimukanova G, Vivona L, Lin M, Lopez E, Callcut R, Srivastava AK, Kornblith LZ, Fields AT, Schreiber MA, Wade CE, Holcomb JB, Pati S

Bone marrow donor selection and characterization of MSCs is critical for pre-clinical and clinical cell dose production.

Journal of translational medicine

Trivedi A, Miyazawa B, Gibb S, Valanoski K, Vivona L, Lin M, Potter D, Stone M, Norris PJ, Murphy J, Smith S, Schreiber M, Pati S

Regulation of Endothelial Cell Permeability by Platelet-Derived Extracellular Vesicles.

The journal of trauma and acute care surgery

Miyazawa B, Trivedi A, Togarrati PP, Potter D, Baimukanova G, Vivona L, Lin M, Lopez E, Callcut R, Srivastava AK, Kornblith LZ, Fields AT, Schreiber MA, Wade CE, Holcomb JB, Pati S

Barriers to clinical research in trauma.

Transfusion

Miskimins R, Pati S, Schreiber M

Multipotent Adult Progenitor Cells, but Not Tissue Inhibitor of Matrix Metalloproteinase-3, Increase Tissue Sparing and Reduce Urological Complications following Spinal Cord Injury.

Journal of neurotrauma

Jones JM, DePaul MA, Gregory CR, Lang BT, Xie H, Zhu M, Rutten MJ, Mays RW, Busch SA, Pati S, Gregory KW

A combat relevant model for the creation of acute lung injury in swine.

The journal of trauma and acute care surgery

Smith S, McCully B, Bommiasamy A, Murphy J, Behrens B, Pati S, Goodman A, Schreiber M

Elevated plasma levels of TIMP-3 are associated with a higher risk of acute respiratory distress syndrome and death following severe isolated traumatic brain injury.

Trauma surgery & acute care open

Hendrickson CM, Gibb SL, Miyazawa BY, Keating SM, Ross E, Conroy AS, Calfee CS, Pati S, Cohen MJ

Platelet-Derived Microvesicles: A Potential Therapy for Trauma-Induced Coagulopathy.

Shock (Augusta, Ga.)

Lopez E, Srivastava AK, Pati S, Holcomb JB, Wade CE

Cellular therapies and stem cell applications in trauma.

American journal of surgery

Wang Y, Pati S, Schreiber M

Mesenchymal stem cell-derived extracellular vesicles attenuate pulmonary vascular permeability and lung injury induced by hemorrhagic shock and trauma.

The journal of trauma and acute care surgery

Potter DR, Miyazawa BY, Gibb SL, Deng X, Togaratti PP, Croze RH, Srivastava AK, Trivedi A, Matthay M, Holcomb JB, Schreiber MA, Pati S

Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis.

Shock (Augusta, Ga.)

Chang R, Holcomb JB, Johansson PI, Pati S, Schreiber MA, Wade CE

Serum from dengue virus-infected patients with and without plasma leakage differentially affects endothelial cells barrier function in vitro.

PloS one

Tramontini Gomes de Sousa Cardozo F, Baimukanova G, Lanteri MC, Keating SM, Moraes Ferreira F, Heitman J, Pannuti CS, Pati S, Romano CM, Cerdeira Sabino E

Lack of species-specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

The journal of trauma and acute care surgery

Peng Z, Pati S, Fontaine MJ, Hall K, Herrera AV, Kozar RA

Plasma Transfusion: History, Current Realities, and Novel Improvements.

Shock (Augusta, Ga.)

Watson JJ, Pati S, Schreiber MA

Wnt3a, a Protein Secreted by Mesenchymal Stem Cells Is Neuroprotective and Promotes Neurocognitive Recovery Following Traumatic Brain Injury.

Stem cells (Dayton, Ohio)

Zhao Y, Gibb SL, Zhao J, Moore AN, Hylin MJ, Menge T, Xue H, Baimukanova G, Potter D, Johnson EM, Holcomb JB, Cox CS, Dash PK, Pati S

Dried plasma: state of the science and recent developments.

Transfusion

Pusateri AE, Given MB, Schreiber MA, Spinella PC, Pati S, Kozar RA, Khan A, Dacorta JA, Kupferer KR, Prat N, Pidcoke HF, Macdonald VW, Malloy WW, Sailliol A, Cap AP

Modulating the endotheliopathy of trauma: Factor concentrate versus fresh frozen plasma.

The journal of trauma and acute care surgery

Pati S, Potter DR, Baimukanova G, Farrel DH, Holcomb JB, Schreiber MA

Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets.

Transfusion

Baimukanova G, Miyazawa B, Potter DR, Muench MO, Bruhn R, Gibb SL, Spinella PC, Cap AP, Cohen MJ, Pati S

The effects of 22°C and 4°C storage of platelets on vascular endothelial integrity and function.

Transfusion

Baimukanova G, Miyazawa B, Potter DR, Gibb SL, Keating S, Danesh A, Beyer A, Dayter Y, Bruhn R, Muench MO, Cap AP, Norris PJ, Spinella P, Cohen M, Pati S

Cellular Therapies in Trauma and Critical Care Medicine: Forging New Frontiers.

Shock (Augusta, Ga.)

Pati S, Pilia M, Grimsley JM, Karanikas AT, Oyeniyi B, Holcomb JB, Cap AP, Rasmussen TE

Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1-/- Mice.

Shock (Augusta, Ga.)

Ban K, Peng Z, Pati S, Witkov RB, Park PW, Kozar RA

TIMP3 Attenuates the Loss of Neural Stem Cells, Mature Neurons and Neurocognitive Dysfunction in Traumatic Brain Injury.

Stem cells (Dayton, Ohio)

Gibb SL, Zhao Y, Potter D, Hylin MJ, Bruhn R, Baimukanova G, Zhao J, Xue H, Abdel-Mohsen M, Pillai SK, Moore AN, Johnson EM, Cox CS, Dash PK, Pati S

Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock.

The journal of trauma and acute care surgery

Potter DR, Baimukanova G, Keating SM, Deng X, Chu JA, Gibb SL, Peng Z, Muench MO, Fomin ME, Spinella PC, Kozar R, Pati S

Syndecan-1 restitution by plasma after hemorrhagic shock.

The journal of trauma and acute care surgery

Kozar RA, Pati S

Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients.

Journal of translational medicine

Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S, Ostrowski SR, Johansson PI, Holcomb JB, Wade CE

The whole is greater than the sum of its parts: hemostatic profiles of whole blood variants.

The journal of trauma and acute care surgery

Kornblith LZ, Howard BM, Cheung CK, Dayter Y, Pandey S, Busch MP, Pati S, Callcut RA, Vilardi RF, Redick BJ, Nelson MF, Cohen MJ

Never-frozen liquid plasma blocks endothelial permeability as effectively as thawed fresh frozen plasma.

The journal of trauma and acute care surgery

Cao Y, Dua A, Matijevic N, Wang YW, Pati S, Wade CE, Ko TC, Holcomb JB

Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: definitions, current practice, and knowledge gaps.

Shock (Augusta, Ga.)

Jenkins DH, Rappold JF, Badloe JF, Berséus O, Blackbourne L, Brohi KH, Butler FK, Cap AP, Cohen MJ, Davenport R, DePasquale M, Doughty H, Glassberg E, Hervig T, Hooper TJ, Kozar R, Maegele M, Moore EE, Murdock A, Ness PM, Pati S, Rasmussen T, Sailliol A, Schreiber MA, Sunde GA, van de Watering LM, Ward KR, Weiskopf RB, White NJ, Strandenes G, Spinella PC

Autologous bone marrow mononuclear cells therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.

The journal of trauma and acute care surgery

Bedi SS, Walker PA, Shah SK, Jimenez F, Thomas CP, Smith P, Hetz RA, Xue H, Pati S, Dash PK, Cox CS

Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1.

Shock (Augusta, Ga.)

Peng Z, Pati S, Potter D, Brown R, Holcomb JB, Grill R, Wataha K, Park PW, Xue H, Kozar RA

Coronary microvascular pericytes are the cellular target of sunitinib malate-induced cardiotoxicity.

Science translational medicine

Chintalgattu V, Rees ML, Culver JC, Goel A, Jiffar T, Zhang J, Dunner K, Pati S, Bankson JA, Pasqualini R, Arap W, Bryan NS, Taegtmeyer H, Langley RR, Yao H, Kupferman ME, Entman ML, Dickinson ME, Khakoo AY

Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective.

Hematology. American Society of Hematology. Education Program

Holcomb JB, Pati S

Spray-dried plasma and fresh frozen plasma modulate permeability and inflammation in vitro in vascular endothelial cells.

Transfusion

Wataha K, Menge T, Deng X, Shah A, Bode A, Holcomb JB, Potter D, Kozar R, Spinella PC, Pati S

Mesenchymal stem cells regulate blood-brain barrier integrity through TIMP3 release after traumatic brain injury.

Science translational medicine

Menge T, Zhao Y, Zhao J, Wataha K, Gerber M, Zhang J, Letourneau P, Redell J, Shen L, Wang J, Peng Z, Xue H, Kozar R, Cox CS, Khakoo AY, Holcomb JB, Dash PK, Pati S

Human mesenchymal stem cells inhibit endothelial proliferation and angiogenesis via cell-cell contact through modulation of the VE-Cadherin/ß-catenin signaling pathway.

Stem cells and development

Menge T, Gerber M, Wataha K, Reid W, Guha S, Cox CS, Dash P, Reitz MS, Khakoo AY, Pati S

Aged plasma transfusion increases mortality in a rat model of uncontrolled hemorrhage.

The Journal of trauma

Letourneau PA, McManus M, Sowards K, Wang W, Wang YW, Matijevic N, Pati S, Wade CE, Holcomb JB

Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock.

PloS one

Pati S, Gerber MH, Menge TD, Wataha KA, Zhao Y, Baumgartner JA, Zhao J, Letourneau PA, Huby MP, Baer LA, Salsbury JR, Kozar RA, Wade CE, Walker PA, Dash PK, Cox CS, Doursout MF, Holcomb JB

Involvement of the glycogen synthase kinase-3 signaling pathway in TBI pathology and neurocognitive outcome.

PloS one

Dash PK, Johnson D, Clark J, Orsi SA, Zhang M, Zhao J, Grill RJ, Moore AN, Pati S

Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation.

PloS one

Haywood-Watson RJ, Holcomb JB, Gonzalez EA, Peng Z, Pati S, Park PW, Wang W, Zaske AM, Menge T, Kozar RA

Increased platelet:RBC ratios are associated with improved survival after massive transfusion.

The Journal of trauma

Holcomb JB, Zarzabal LA, Michalek JE, Kozar RA, Spinella PC, Perkins JG, Matijevic N, Dong JF, Pati S, Wade CE, Holcomb JB, Wade CE, Cotton BA, Kozar RA, Brasel KJ, Vercruysse GA, MacLeod JB, Dutton RP, Hess JR, Duchesne JC, McSwain NE, Muskat PC, Johannigamn JA, Cryer HM, Tillou A, Cohen MJ, Pittet JF, Knudson P, DeMoya MA, Schreiber MA, Tieu BH, Brundage SI, Napolitano LM, Brunsvold ME, Sihler KC, Beilman GJ, Peitzman AB, Zenati MS, Sperry JL, Alarcon LH, Croce MA, Minei JP, Steward RM, Cohn SM, Michalek JE, Bulger EM, Nunez TC, Ivatury RR, Meredith JW, Miller PR, Pomper GJ, Marin B

Increased transforming growth factor ß contributes to deterioration of refrigerated fresh frozen plasma's effects in vitro on endothelial cells.

Shock (Augusta, Ga.)

Duan C, Cao Y, Deng X, Wang W, Yang W, Liu X, Chen Z, Pati S, Kozar RA, Gonzalez EA, Wade CE, Holcomb JB, Ko TC

Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock.

Anesthesia and analgesia

Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, Ko TC, Paredes A

Human Bone Marrow Derived Mesenchymal Stem Cells Regulate Leukocyte-Endothelial Interactions and Activation of Transcription Factor NF-Kappa B.

Journal of tissue science & engineering

Letourneau PA, Menge TD, Wataha KA, Wade CE, S Cox C, Holcomb JB, Pati S

Human mesenchymal stem cells inhibit vascular permeability by modulating vascular endothelial cadherin/ß-catenin signaling.

Stem cells and development

Pati S, Khakoo AY, Zhao J, Jimenez F, Gerber MH, Harting M, Redell JB, Grill R, Matsuo Y, Guha S, Cox CS, Reitz MS, Holcomb JB, Dash PK

Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes.

Journal of molecular and cellular cardiology

Rogers TB, Pati S, Gaa S, Riley D, Khakoo AY, Patel S, Wardlow RD, Frederick CA, Hall G, He LP, Lederer WJ

Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: preserving the blood brain barrier via an interaction with splenocytes.

Experimental neurology

Walker PA, Shah SK, Jimenez F, Gerber MH, Xue H, Cutrone R, Hamilton JA, Mays RW, Deans R, Pati S, Dash PK, Cox CS

Fresh frozen plasma increases adhesion molecule expression on human pulmonary endothelial cells.

The Journal of surgical research

Letourneau PA, Pati S, Gerber MH, Jimenez F, Holcomb JB

Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress.

The Journal of clinical investigation

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

HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation.

Virology

Yadav A, Pati S, Nyugen A, Barabitskaja O, Mondal P, Anderson M, Gallo RC, Huso DL, Reid W

Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma.

The Journal of experimental medicine

Khakoo AY, Pati S, 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, Frank JA, Reitz M, Finkel T

Suppression of MIP-1beta transcription in human T cells is regulated by inducible cAMP early repressor (ICER).

Journal of leukocyte biology

Barabitskaja O, Foulke JS, Pati S, Bodor J, Reitz MS

Tumorigenesis by human herpesvirus 8 vGPCR is accelerated by human immunodeficiency virus type 1 Tat.

Journal of virology

Guo HG, Pati S, Sadowska M, Charurat M, Reitz M

Human herpesvirus 8-encoded vGPCR activates nuclear factor of activated T cells and collaborates with human immunodeficiency virus type 1 Tat.

Journal of virology

Pati S, Foulke JS, Barabitskaya O, Kim J, Nair BC, Hone D, Smart J, Feldman RA, Reitz M

Antitumorigenic effects of HIV protease inhibitor ritonavir: inhibition of Kaposi sarcoma.

Blood

Pati S, Pelser CB, Dufraine J, Bryant JL, Reitz MS, Weichold FF

Human herpesvirus 8 K1-associated nuclear factor-kappa B-dependent promoter activity: role in Kaposi's sarcoma inflammation?

Journal of the National Cancer Institute. Monographs

Samaniego F, Pati S, Karp JE, Prakash O, Bose D

Urinary proteins with pro-apoptotic and antitumor activity.

Apoptosis : an international journal on programmed cell death

Pati S, Lee Y, Samaniego F

HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells.

Journal of human virology

Weichold FF, Bryant JL, Pati S, Barabitskaya O, Gallo RC, Reitz MS

Gain of function mutations in p53.

Nature genetics

Dittmer D, Pati S, Zambetti G, Chu S, Teresky AK, Moore M, Finlay C, Levine AJ