Innovations in surgery at Ohio State


The Department of Surgery's research efforts are focused on key areas of interest that promise to yield significant results in the understanding of disease and the improvement of clinical care. The department's stature and the reputation of its researchers and clinicians enable it to receive significant funding from private industry and federal sources, such as the National Institutes of Health.

Areas of research

Research efforts continue to focus on three major areas – wound healing, vascular biology/transplantation and tumor biology.

Cardiovascular disease and stroke

Antiplatelet medications

Researchers at The Ohio State University Wexner Medical Center examined the use of an investigative intravenous antiplatelet drug, Cangrelor, and found it to be an effective bridge between long-lasting oral antiplatelet medications and cardiac surgery. The drug’s platelet inhibition rapidly loses effect within a few hours, so it can be discontinued just prior to surgery. Results of the study are available in the January 18, 2012 edition of the Journal of the American Medical Association. In the study, 210 patients at 34 international medical centers including Ohio State were randomized to stop oral antiplatelet therapy and receive either intravenous Cangrelor or placebo for up to five days prior to coronary artery bypass surgery. Treatment stopped approximately three hours before incision. Researchers found patients treated with Cangrelor maintained a low risk of clotting complications from platelet deactivation without a significant excess in bleeding or bleeding complications, compared to those on placebo.

Stroke

Stroke is the fourth leading cause of death in the U.S. and the leading cause of long-term disability. Department of Surgery faculty are uncovering new means and mechanisms to protect brain tissue from stroke injury. One such approach employs dietary supplementation with a lesser characterized vitamin E analog not found in Western diet called alpha-tocotrienol (TCT). Investigators have identified both neuro- and vascular-protective properties of this unique natural form of vitamin E that significantly protects brain tissue against stroke-induced injury. This multi-modal approach to protection is strengthened by a safety profile of a natural vitamin that enables combining treatment with standard of care therapies for stroke survivors. A second line of investigation by researchers in the Department of Surgery has uncovered mechanisms to turn otherwise neurotoxic molecules released in the brain during stroke into a source of energy that sustains neuron cell survival. Here, investigators identified an enzyme called glutamate oxaloacetate transaminase (GOT) that lowers cell death-inducing levels of glutamate in the brain during stroke by converting it into a source of cellular energy. Studies are now underway to identify novel small molecules that increase expression and activity of GOT for better protection against stroke injury.

Infection and inflammation

Infection

Infection is a common complication of chronic ulcers. Biofilms are estimated to account for 60 percent of chronic wound infections. In biofilm, bacteria are encased within extra polymeric substance (EPS) and become recalcitrant to antimicrobials and host defenses. Using a preclinical swine model of mixed species wound biofilm infection, an unusual observation was made that although biofilm infection may or may not influence the rate of wound closure as measured by standard planimetry, it inevitably compromises the functional property of the repaired skin. The wound may close as evaluated visually, but that closed wound lacks barrier function. Such pathology is caused by the perturbation of epithelial junctional proteins in response to biofilm infection. The wound biofilm infection program funded by multiple awards from NIH NINR is investigating host-biofilm infection interactions and underlying mechanisms of such interactions.

Inflammation

Inflammation is a self-protecting immune response of the body against harmful stimuli in an attempt to eliminate the stimuli and initiate the healing cascade. Diabetic ulcer is a serious complication associated with type 2 diabetes mellitus. A chronic inflammatory state is a characteristic feature of these ulcers. Resolution of inflammation is a dynamically regulated process – the timeliness of which has major bearing on healing outcomes. Macrophages are highly plastic, dynamic and heterogeneous cells that are major regulators of inflammatory response at an injury–site. The diabetic wound healing program funded by NIH NIDDK is investigating the role of macrophage plasticity and phenotypes in diabetic ulcers.

Injury and critical illness

Injury and critical illness

Research led by Dr. Stanislaw Stawicki, includes:
  • Damage control surgery and open abdomens
  • Comorbid conditions and polypharmacy in trauma patients
  • Patient safety topics including retained surgical items
  • Respiratory failure and mechanical ventilatory support
  • Clinician-performed bedside ultrasonography
  • Surgical complications and related topics
  • The introduction of the comorbidity-polypharmacy Score
In the area of ultrasonography and hemodynamic monitoring, a prospective study of novel approaches that has the potential to make intravascular volume status assessments using bedside ultrasound significantly easier than currently available techniques.

Surgical damage control and open abdomens represents the most promising area for the development of translational research models. In conjunction with Dr. Bergese (Department of Anesthesiology), Dr. Stawicki is currently developing a collaborative basic science model that will examine neuro-endocrine changes occurring with repeated episodes of general anesthesia in critically ill surgical patients.

The comorbidity-polypharmacy score (CPS) is a novel yet simple clinical tool. Over the last three years, the CPS was found to be a good predictor of mortality, morbidity and survival in trauma patients. It was also identified as a potential trauma triage tool. Currently, researchers are applying the CPS to non-trauma populations in order to define its utility as a marker of morbidity, mortality and other important measures such as hospital readmissions.

Transplantation and immunology research

Transplantation and immunology research

The Division of Transplantation is dedicated to building upon a solid foundation of basic, translational and clinical research in order to define and develop the next generation of high quality, comprehensive and cost-effective transplant programs.

Research programs

View our research programs in the Department of Surgery.

  • Transplant rejection
  • Allograft acceptance and transplant tolerance
  • Novel immunologic strategies for islet cells transplantation 
  • Cellular transplantation
  • New immunosuppressive compounds

Research interests

Gregg A. Hadley, PhD

  • The immunologic mechanisms of renal allograft rejection and graft-vs-host disease pathology and the development of novel therapeutic strategies for intervention in these processes
  • Use of nanotechnology to measure immunomodulatory analytes in real time in organ transplant recipients
  • Development of novel processes to enable transplantation of pancreatic islet xenografts into human diabetics

Ronald Pelletier, MD

  • The immunobiology of graft acceptance and the role of alloantibodies in allograft pathobiology
  • The relationship between cellular and humoral donor-specific immunologic recognition and post-transplant outcomes

Ginny Bumgardner MD, PhD

  • Continues her investigations in transplant immunobiology, using experimental models of pancreatic islet and hepatocyte (liver cell) transplantation

Amer Rajab, MD, PhD

  • The development of novel strategies to enable transplantation of pancreatic islets into non-human primates and the development of novel strategies for successful transplantation of islet xenografts in the non-human primate model
Kenneth Andreoni, MD
  • Development of mathematical models for unbiased prediction of tissue typing results to facilitate national sharing of cadaver kidneys
  • New anti-rejection drugs
  • Antibody-mediated injury to liver and kidney grafts


Accomplishments in research

Gregg A. Hadley, PhD, serves as the deputy director of research in the Comprehensive Transplant Center. He leads a research program focused on defining mechanisms of chronic tissue injury following transplantation and the development of novel therapeutic strategies for intervention in these processes.

Dr. Ronald Pelletier continues the division’s investigations into the immunobiology of graft acceptance and the role of alloantibodies in allograft pathobiology. Our recent studies addressing transplantation tolerance suggest that allograft acceptance may evolve through a series of mechanisms involving TGFb and foxP3 regulatory cells. These mechanisms are associated with donor-reactive alloantibodies and pathology within the grafts, and do not lead to true transplantation tolerance, despite the ability to accept donor matched skin allografts. Our ongoing studies of the role of alloantibodies in transplantation reveal that alloantibodies are not necessarily directed at MHC molecules, but are also directed at tissue associated and tissue-specific molecules. Using new experimental assays for alloantibody detection, our studies have further revealed that some, but not all, of these antibodies are complement-fixing. Investigational studies focusing on humoral allograft rejection in an animal model are designed to carefully characterize the acute inflammatory events leading to antibody-mediated graft damage. We hope to define stages in the process that offer opportunities for therapeutic intervention to ameliorate graft damage.

Translational Research in Immunologic Recognition and Post-transplant Outcomes

Dr. Ronald Pelletier continues his translational research (basic, tissue typing and clinical) investigating the relationship between cellular and humoral donor-specific immunologic recognition and post-transplant outcomes. Efforts are now under way to foster living donor/recipient pair exchanges to enable increasing numbers of patients to obtain a lifesaving kidney transplant. Additionally, methods for removing circulating alloantibodies in sensitized recipients to permit safe organ transplantation continue to be investigated.

Transplantation Immunobiology

Dr. Ginny Bumgardner continues her investigations in transplant immunobiology, using experimental models of pancreatic islet and hepatocyte (liver cell) transplantation. Dr. Bumgardner’s lab-based research focuses on basic mechanisms of alloimmune mediated hepatocyte injury. She introduced the functional hepatocyte transplantation model using transgenic hepatocytes to study the in vivo immunobiology of allogeneic hepatocellular transplantation in 1998. 

Published work demonstrates that allogeneic hepatocytes are vulnerable to cell-mediated as well as alloantibody-mediated parenchymal cell damage. Her studies using this model in comparison to genetically matched islet transplant and heart transplant, have demonstrated the importance of tissue (parenchymal cell type) in determining the phenotype and effector mechanisms comprising alloimmune responses after transplantation. Work from her lab has demonstrated that allogeneic liver parenchymal cells stimulate the maturation of CD4-independent and CD4-dependent allospecific CD8+ cytolytic effectors (allo-CTLs). This pathway is important because it can cause transplant tissue damage, either early or late after transplant, and interferes with the induction of transplantation tolerance. These CTL subsets are distinct in magnitude of in vivo cytotoxic effector function, CD8+ T cell recall responses in vivo and molecular effector mechanisms, which mediate cytotoxicity. 

Furthermore, these two pathways are differentially susceptible to conventional and experimental immunosuppressive agents. Dr. Bumgardner’s laboratory was the first to report the efficacy of a novel immunosuppressive strategy that successfully suppresses this immunoresistant (CD4-independent) CD8+ T cell mediated immune pathway and promotes long-term allograft survival. Very little is known regarding how CD8+ T cells cause immune damage of allografts and in vivo effector functions of alloreactive CD8+ T cells is a specific focus for investigation. 

Dr. Bumgardner’s lab is also investigating CD4-dependent humoral immune pathways of allograft damage. Her lab is the first to show that alloantibodies also mediate immune damage of transplanted hepatocytes by a macrophage-dependent, complement-independent, NK-independent cytotoxic effector mechanism. Studies are ongoing to investigate novel mechanisms governing the regulation of post transplant alloantibody production in an animal model and to investigate translational aspects of these studies in humans. These and other projects have been funded by external sponsors, such as the American Diabetes Association, the Roche Organ Transplant Research Foundation, the American Society of Transplant Surgeons, the American Society of Transplantation and the National Institutes of Health.

Research in regenerative medicine

First Technology for Non-Viral In Vivo Tissue Reprogramming

This technology is the first to bring tissue reprogramming to point of care application (Nature Nanotechnology 2017).

Membrane repair process in action

This video depicts the membrane repair role that MG53 manages within the cell. GFP fused with MG53 (GFP-MG53) allows tracing of the membrane repair process following injury created by penetration of a microelectrode. Rapid movement of GFP-MG53 (green fluorescence) is observed at the site of the puncture where the repair patch is formed. When severe damage is inflicted on the membrane, MG53 can seal the rupture to allow survival of the cell.

Research by division or center

Research by division or center