The Department of General Surgery is actively engaged in performing high quality bench, translational and clinical research to apply scientific method in order to provide greater understanding and insight of the physiology and pathophysiology of a range of human disease states. These goals are achieved through physicians and scientists working in close collaboration. In addition to the Department’s research endeavors, the staff and faculty are actively engaged in the teaching and training of physicians and scientists throughout the different stages of their career development.
Mission Statement: To identify clinically relevant disease problems that can be investigated in the laboratory using appropriate translational models of the disease state.
Hepatocellular Carcinoma (HCC) Cancer Biology- Liver Pathology
Hepatocellular Carcinoma (HCC) Translational Research
Surgical Oncology-Cancer Biology-Melanoma
Trauma and Surgical Critical Care
Hepato-biliary and Pancreatic Surgery
Division of Gastrointestinal and Minimally Invasive Surgery
Acute Renal Failure Research
I. Hepatocellular Carcinoma (HCC) Cancer Biology-Liver Pathology
Iain H. McKillop, PhD, Director for Research
Dr. McKillop’s group studies the pathogenesis of liver diseases that culminate in the development and progression of hepatocellular carcinoma (HCC). To achieve these goals, the laboratory makes extensive use of in vitro cell biology techniques to try and better understand the aberrations in signal transduction pathways that occur in HCC that drive cell tumorgenicity. These studies are particularly interested in the processes of transformation, whereby normal cells become cancerous cells, and how these transformed cells subsequently progress to form tumor masses. Many of these studies address fundamental characteristics of hepatic tumor cells: the increased rate of cell growth that is observed following transformation, the inability of transformed cells to perform the normal physiological functions of the parent cells, and the (relative) resistance of cancerous cells to die. These studies are complimented by in vivo studies in which relevant animal models are used to mimic the human disease states to better understand disease pathology and progression. These models provide important insight into how systemic stressors such as chronic, heavy alcohol consumption and obesity impact liver disease and HCC development. These studies are performed in close collaboration with Drs. Iannitti, Martinie, Swan (HPB Surgery) and Russo and DeLamos (Hepatology), clinicians in the Departments of Surgery and Medicine.
Eugene Sokolov, PhD, Senior Postdoctoral Fellow. Dr. Sokolov’s work focuses on the role of lysophosphatidic acid (LPA) signaling within the context of HCC. LPA signaling has proven somewhat of an anomaly in liver physiology and pathology since the liver is known to be involved in producing and regulating LPA synthesis yet it does not express receptors for LPA. Dr. Sokolov was the first to report that the liver expresses a newly characterized receptor for LPA; LPAR6, and that the expression and function of LPAR6 is altered in HCC. These data will provide critical data regarding the function of novel pathways in regulating normal signaling in healthy liver and potential insight and targets for intervention in diseased liver in which the fidelity of these pathways is altered.
Kyle Thompson, PhD, Senior Postdoctoral Fellow. Dr. Thompson’s work addresses the impact of obesity as both a risk factor for HCC development and a co-morbid factor for disease progression. These studies employ state-of-the art molecular and cell biology techniques to mimic human disease states and unique, translational animal models. These studies have allowed Dr. Thompson to identify fatty acid binding proteins (FABPs; proteins that are integral to normal fat uptake and movement in healthy liver cells) as unique targets that become disrupted in hepatic tumors that form in the liver in the setting of morbid obesity. Dr. Thompson is also integrally involved in the development and training of the HPB Fellowship program where he works in tandem with Dr. Swan to provide a comprehensive research and clinical training program for the Fellows.
Valentina Zuckerman, PhD, Postdoctoral Fellow. Dr. Zuckerman is engaged in studying the role of G-protein coupled signaling in normal liver physiology and liver pathology. These studies focus on how intracellular signaling pathways in the liver become unbalanced when placed under physiological stress. In effect, changing how the cell communicates internally affects not only net cell function, but how the cell subsequently responds to external stimuli. Dr. Zuckerman works closely with Drs. Sokolov and McKillop to study the regulation and dysregulation of signaling pathways in HCC development and progression.
Ramanathan Seshadri, MD, HBP Fellow. Dr. Seshadri has recently completed the first year of his training as a HPB Fellow in which he was actively engaged in translational and clinical research projects in support of the Division of HPB Surgery. Dr. Seshadri has now commenced his clinical training year with Drs. Iannitti, Martinie, and Swan (HPB Surgery). Dr. Seshadri’s research area was particularly focused studies that analyzed patient outcomes for those undergoing surgical procedures for cancers of the liver, biliary system, and pancreas and worked closely with Dr. Thompson to study the impact of obesity on the incidence of HCC and rate of disease progression.
Erin Hanna, MD, HBP Fellow. Dr. Hanna recently graduate from the residency program at CMC and has begun the first year (Research Year) of her HPB Fellowship training. Dr. Hanna will work with Drs. McKillop and Thompson to study the interaction of obesity and chronic, heavy alcohol intake on HCC. These studies will incorporate animal models of tumor development and progression and will be performed in parallel with outcomes based research for patients presenting with HCC and the different etiologies and underlying pathologies associated with these groups.
Shayan Nazari, BS, Masters Student. Ms Nazari is the newest recruit to the research group and was recently accepted to the Masters degree program at UNC at Charlotte. Ms. Nazari will work with Dr. Thompson, under the supervision of Drs. McKillop (CMC) and Dr. Richardson (Department of Biology, UNCC), in pursuit of her graduate degree. Her project will focus on developing novel models with which to study chronic and binge alcohol consumption and the mechanisms that drive the pathogenesis associated with alcoholic liver disease.
II. Hepatocellular Carcinoma (HCC) Translational Research
Iain H. McKillop, PhD, Director for Research
Dr. McKillop’s group collaborates with surgeons from the HPB Division (Drs. Iannitti, Martinie, and Swan) and Drs. El Ghannam (UNC at Charlotte) and Davalos (VA Tech) to develop novel approaches to treat HCC. These studies involve working closely with industry partners and start-up biotechnology companies to improve existing technology to perform more accurate and efficient tumor destruction (ablation) in situ. In addition they are interested in developing novel irreversible electroporation (IRE) ablation strategies that will prove to be highly efficient in destroying tumors while limiting the damage to underlying non-tumor tissue. These studies are also interested in developing novel techniques to deliver focused high doses of chemotherapeutic agents directly within the tumor mass while restricting the intra and extra-hepatic side effects. This is particularly important in the treatment of HCC due to role of the liver in drug metabolism and the compromised liver function of many of the patients that present with HCC. To achieve these goals Dr. McKillop is working with Dr. El Ghannam and Dr. Iannitti to develop bioceramic nanonscaffolds as a customizable drug delivery platform for treating HCC. This work was most recently sponsored by a multi-institutional research grant from the NC Biotechnology Center.
Jacob Swet, MS, Research Technician. Mr. Swet is a technician in the Department of Surgery and plays a pivotal role in coordinating the research efforts on the bioceramic project. This includes helping to analyze the kinetics of drug release from bioceramic nanoscaffolds and establishing the in vivo models of hepatic ablation and drug delivery. Mr. Swet works closely with researchers, clinicians and industry groups to design and develop appropriate animal models as well as the collection, analysis and preparation of data during and after study completion.
III. Surgical Oncology-Cancer Biology- Melanoma
David M. Foureau, PhD, Research Scientist
The Surgical Oncology Research group is led by Drs. Foureau, White and Salo, and has a particular focus on studying melanoma, the most common type of skin cancer that arises from transformation of melanocytes. At present immunotherapy represents the most effective therapeutic approach to treat late stage melanoma, where the tumor has metastasized to distant organs but is effective in only 10-20 percent of patients. The Surgical Oncology Research group employs experimental models of melanoma to identify novel cellular and molecular immune mechanisms associated with responsiveness to immunotherapy. A central component of the research efforts includes collaboration with Drs. White, Amin and Salo (clinicians at the Levine Cancer Institute) to identify the hallmark(s) of such immune bias. In doing so, we aim to identify early biomarkers that will allow us to measure (or predict) patient responsiveness to immunotherapy, and develop new immunotherapeutic strategies that will restore immune potency against the cancer cells. This work is enhanced by clinical research that allows for detailed analysis of patient and treatment outcomes from which we will be able to better asses therapeutic strategies and integrate outcomes with clinical and research data. This component of the research effort is led by Drs. White and Salo, assisted by Kendal Carpenter.
These studies are currently sponsored, in part, by research grants from the Purple Promise Foundation to End Melanoma
IV. Trauma and Surgical Critical Care
Toan Huynh, MD, Director for Trauma and Surgical Critical Care Research
The Trauma and Surgical Critical Care Research group works within the Department of Surgery to study the physiological and pathological responses to hemorrhagic shock and reperfusion (HSR) injury and septic shock. These studies focus primarily on the role of mitochondrial dysfunction and the progression to multiple organ failure (MOF) following exposure to severe systemic stress induced by either massive blood loss or infection (sepsis). To achieve these goals, we utilize in vitro models of hypoxia and sepsis along with clinically relevant in vivo models to mimic the human disease states.
Our most recent studies have concentrated on developing novel therapeutic interventions based on mitochondrial-targeted antioxidants. Previous studies have identified reactive oxygen species (ROS) as key modulators of the inflammatory response following HSR or sepsis. Under normal physiological conditions the mitochondria produce ROS in small quantities allowing endogenous antioxidant mechanisms to remove them. However, following exposure to rapid and severe physiological or pathological stress the normal antioxidant pathways become swiftly overwhelmed, and the electron transport chain in the mitochondria breaks down. It thus makes sense, that therapies targeted to the primary source of ROS production (the mitochondria) may offer enhanced protection against the deleterious effects of ROS when compared to conventional cytoplasmic therapies.
These studies are being performed in collaboration with Drs. Susan Evans and Toan Huynh, surgeons in the Department of Trauma, Surgical Critical Care and Acute Care Surgery.
V. Hepato-biliary and Pancreatic Surgery
David Iannitti, MD, Chief, Hepato-biliary and Pancreatic Surgery
Srikanth Padma MD, HBP Fellow. As a fellow, Dr. Padma is actively engaged in basic and translational research projects before commencing his clinical training year. Dr. Padma’s research area is studying the expression and localization of aquaporin water channels in healthy, diseased and tumorigenic liver samples in the setting of the human disease state as a means to better understand the multiple stages of cell transformation and tumor progression.
Jessica Heath, BS, Research Laboratory Technician. Ms. Heath works for Dr. Iannitti in establishing large animal models with which to develop and characterize microwave ablation techniques and assists in the development and analysis of samples generated using these models.
VI. Division of Gastrointestinal and Minimally Invasive Surgery
B. Todd Heniford, MD, Chief, Division of Gastrointestinal and Minimally Invasive Surgery; Co- Director, Carolinas Laparoscopic and Advanced Surgery Program; Director, Carolinas Hernia Medical Center
Amy Lincourt, PhD, Senior Scientist, Director of Research Operations, Division of Gastrointestinal and Minimally Invasive Surgery
Jennifer E. Keller, MD, Research Fellow
Charles James Dolce, MD, Minimally Invasive Surgery Fellow
Kenneth Christian Walters, MD, General Surgery Research Resident
VI. Acute Renal Failure Research
Susan Evans, MD, Principal Investigator, Acute Renal Failure Research
James Tumlin, MD, South East Renal Associates. Dr. Tumlin is a clinical nephrologist working with Southeast Renal Associates with basic science research interests in identifying and analyzing the expression of potential markers of acute renal failure. Dr. Tumlin and Dr. Evans work closely in the development of this project and identifying patients for inclusion in this study.
Jarrod Meadows, BS, Southeast Renal Associates. Mr. Meadows performs the hands on experimental analysis of serum and urine obtained from patients enrolled in the current series of studies and, works with Dr Evans in the collection and analysis of data generated from these studies.
Senait Testafi, BS. Ms. Testafi performs protein analysis in urine pellets collected from patients enrolled in the current study for potential markers that may be of use in identifying ARF in at risk patient populations.
Hepatocellular Carcinoma (HCC) Cancer Biology -Liver Pathology: Iain McKillop, PhD
Hepatocellular Carcinoma (HCC) Translational Research: Iain McKillop, PhD
Surgical Oncology-Cancer Biology- Melanoma: David Foureau, PhD
Trauma and Surgical Critical Care: Toan Huynh, MD
Hepato-biliary and Pancreatic Surgery: David Iannitti, MD
Division of Gastrointestinal and Minimally Invasive Surgery: B. Todd Heniford, MD; Amy Lincourt, PhD
Acute Renal Failure Research: Susan Evans, MD