Optional Research Years

Current Research Opportunities

• Surgical Education Research Fellowship

  The Surgical Education Research Fellowship in the Department of Surgery was established in 2017 and aims to develop education leaders who will contribute to the advancement of surgical education at IU and nationally through innovation and high impact research output. The fellows work under the mentorship of Dimitrios Stefanidis, MD, PhD and E. Matthew Ritter, MD, MPHE, and are part of a larger education research group that includes surgical educators such as the residency and skills lab directors, research coordinators, research residents, international research fellows, the anesthesia director of education, medical students and other collaborators.

  During the program, fellows expand their knowledge and skills in surgical education and engage in challenging and data-driven education research and teaching activities. Fellows are expected to lead innovative research projects within the Department of Surgery and School of Medicine and produce several high-quality presentations, publications and grant submissions. This two year experience provides fellows with the necessary skills, support and a nurturing environment to empower them to excel in education research and become surgical education leaders. 

• Global Health Fellowship with Department of Surgery and AMPATH

  Participants in the Masters in Public Health in Global Health program spend the first year completing Master’s in Public Health classwork and the second year at Moi University in Eldoret, Kenya. Due to the course workload, residents in this program are not be required to participate in lab work during the first year. The second year may require six to nine credit hours to be completed online, but residents work with JoAnna Hunter-Squires, M.D. during the second year in pursuit of research in the realm of surgery and global health.

  Participants are eligible to apply for Fulbright Scholar status with this fellowship.

• Laboratory of Andrea Bonetto, PhD, General Surgery

  The Bonetto lab primarily focuses on understanding the mechanisms of cancer- and chemotherapy-derived muscle wasting (i.e. cachexia). Our ultimate goal is to identify novel markers and new therapies to improve the quality of life in cancer patients. Our previous studies have suggested that cancer and chemotherapy affect muscle mass by substantially causing mitochondrial depletion and promoting abnormal energy metabolism. In addition, we observed derangements of neuromuscular junction integrity, which may contribute to the onset of muscle weakness and fatigue. We believe that preservation of the mitochondrial pool by using molecular and/or pharmacologic approaches will improve muscle size and function and will contribute to restore the proper energy metabolism in a setting of cancer or following chemotherapy treatment.

  Additional areas of focus include:

  • Generation and characterization of novel experimental models for the study of cancer cachexia. In the past we have contributed to establish a new model of ovarian cancer-induced cachexia that we have fully characterized in terms of musculoskeletal complications. We are currently characterizing new models of metastatic colorectal cancer-induced cachexia.
  • Study of the muscle and bone crosstalk in models of cancer- and chemotherapy-induced cachexia. Our preliminary evidence suggests that muscle and bone exchange biochemical factors responsible for both muscle atrophy and bone loss.
  • Characterization of cachexia in muscle from patients affected with head and neck cancer undergoing free-flap reconstruction (collaboration with Otolaryngology).
• Laboratory of Burcin Ekser, MD, PhD, Transplant Surgery

  The Xenotransplantation Research laboratory (Ekser Lab) has a long history at the Department of Surgery, IUSM. The lab has been very productive over the last decade focusing on inter-species immunology, coagulation dysregulation, genetic engineering, and the production of genetically-engineered pigs, having published several seminal papers with the help of students, residents and post-doctoral researchers. As an active transplant and immunology lab, we are engaged in translational projects focused on transplant immunology, creation of desirable genetic combination in porcine cells, which can be used to generate suitable organs for xenotransplant (e.g. Gal-knockout, CMAH gene-knockout, B4GalNT2 gene knockout pigs). We have recently identified for the first time porcine tetraspanins CD37 and CD81 as novel nonGal xenoreactive antigens.

  Most recently, we have also introduced the use of ‘scaffold-free’ 3D-bioprinting of genetically-engineered pig cells, as well as human (normal and/or cancer) cells with the help of 3D-Bioprinting Core of IUPUI. We have so far bioprinted porcine liver models using the 3D-Bioprinter and presented at the Joint IUPUI-Johns Hopkins University 3D-Bioprinting Symposium and at the International Xenotransplantation Association Meeting. On a daily basis, we are engaged in identifying novel xenoantigens using genetic engineering (CRISPR/cas9), immunology, coagulation dysregulation (Chronolog Aggregometer Technology) and 3D-bioprinting of porcine and/or human cells.

• Laboratory of Gayle Gordillo, MD, Plastic Surgery IB 447

  The Gordillo lab has been NIH funded for the past 12 years to study mechanisms regulating hemangioma growth. Hemangiomas are endothelial cell tumors and they are the most common soft tissue tumor of infancy. The lab uses a validated murine model of endothelial cell tumors that utilizes tumor forming endothelial (Eoma) cells derived from a spontaneously arising hemangioendothelioma tumor in 129 P/3 mice. These cells can be used for in vitro mechanistic studies, but they also form hemangioendothelioma tumors when injected subcutaneously into mice for in vivo experiments. Mice die of Kassabach-Merritt phenomenon at 10-14 days effectively recapitulating the same condition observed in humans with hemangioendothelioma tumors. We have shown that the mechanisms that promote hemangioendothelioma growth are shared by hemangiomas and collectively refer to both tumors as HE. Current pharmacologic treatments for hemangioma are associated with high risk side effect profiles limiting the number of affected children that can receive treatment. The lab is focused on developing novel therapies that disrupt the mechanisms that drive HE tumor formation. We will also investigate whether the mechanisms that drive HE tumor formation are shared by other endothelial and non-endothelial tumors.

• Laboratory of Al Hassanein, MD, MMSc, Plastic Surgery

  The lab is focuses on two projects (1) lymphedema and (2) breast implant capsular contracture. Lymphedema is a morbid disease most often breast cancer related. There is no cure and it is characterized by chronic, progressive limb enlargement. Capsular contracture is a disease of scar/fibrosis of breast implants characterized clinically by distortion and pain. The goals of the lab are to determine the molecular etiology of lymphedema and the pathogenic basis of capsular contracture. Both projects involve translational research analyzing surgical specimen. The lymphedema study also comprises a rodent tail model. The lab is a collaboration with Dr. Mithun Sinha and Dr. Chandan Sen of the Indiana Center for Regenerative Medicine and Engineering.

• Laboratory of Savita Khanna, PhD

  Dr. Savita Khanna’s lab has long-standing experience in conducting and leading in vitro and in vivo studies related to mechanisms of tissue injury and interventional rescue. One of the key areas being investigated by Khanna’s laboratory is brain injury, including neurodegeneration and therapeutics. Another major project in her lab focuses on diabetic peripheral neuropathy and modes of rescuing the condition. To address scientific questions related to ongoing projects, the lab is using both in vitro (cell lines and primary cells culture) and in vivo models.

• Laboratory of Leonidas Koniaris, MD, and Teresa Zimmers, PhD

  Under the direction of Leonidas Koniaris, MD and Teresa Zimmers, PhD, the Cachexia Lab studies mechanisms of tissue growth control and systemic adaptation to acute or chronic organ injury. In practice this has led to a focus on organ injury and regeneration and the pathological perversion of that process—cancer, and the effects of those processes on distant tissues, particularly skeletal muscle and adipose tissue, but also liver, bone and the hematopoietic compartment. We are particularly interested in how growing organs and tumors signal on liver, muscle and adipose tissue to change their metabolism and yield substrates for growth, including amino acids and fatty acids. A regenerating liver or skin burn requires the catabolism of striated muscle and fat—proteolysis and lipolysis, as well as bone loss, in order to fuel the innate immune response and cell proliferation and healing. Some tumors, particularly pancreatic cancer, pervert this adaptive response and lead to a maladaptive and ultimately fatal wasting syndrome. Understanding the cross-talk among the injured organs/tumor and the periphery will allow us to identify targets to manipulate and prevent systemic wasting and debilitation and accelerate recovery after injury and in patients with cancer.

  The laboratory’s research spans cultured cell models to mouse models of human disease to translational studies using prospectively collected human data and specimens. Directed studies interrogating specific pathways are balanced with discovery approaches generated through transcriptomic and proteomic assays. The lab is newly engaged in the identification of small molecules that influence muscle wasting and cachexia, and the production of biologics to inhibit specific protein targets. Pathways of interest include the hedgehog/SMO/GLI, Hippo/YAP, IL-6 family of cytokines, the TGF-beta superfamily and other secreted and circulating growth factors, and lipid modulators of cell growth and wasting.

• Laboratory of Chandrashekar Kubal, MD

  The mission of the Kubal translational research laboratory is to improve liver transplant outcomes. The laboratory is one aspect of a multidiscipline group of professionals focused on advancing treatments for liver disease. The research within the Kubal laboratory focuses on important complications after liver transplantation, mainly as a result of ischemia reperfusion injury of the liver. Some of the aspects of this phenomenon are being addressed in clinical research with the use of normothermic machine perfusion of human livers as a multicenter clinical trial. However, in the laboratory we are focusing on the remote kidney injury as a result of liver ischemia reperfusion injury.

  Additionally, the liver transplant program has a large database that includes more than 2000 liver transplant patients, which is used extensively for clinical research.
  Dr. Kubal's  clinical trials include immunosuppression related trials.

• Laboratory of Troy A. Markel, MD, Pediatric Surgery

  The Markel lab has been in existence for the last seven years and primarily focuses on finding novel therapies for the treatment of intestinal ischemia and necrotizing enterocolitis. The primary focus is on stem cell therapy for treatment, and understanding the mechanistic pathways that these cells utilize to bring about end organ protection. Our previous studies have suggested that stem cells can decrease mortality by nearly 60 percent in animal models following intestinal ischemia. In addition, stem cells appear to improve intestinal perfusion, limit mucosal injury, improve tight junction integrity and limit the local inflammatory process. We believe that these cells protect the bowel by releasing key paracrine mediators, such as hydrogen sulfide gas, that work to promote mesenteric vasodilation by interacting with the nitric oxide signaling pathway.

  Additional areas of focus include the differences between adults and children in their response to trauma. There appears to be a loss of childhood protective effects in the adult response to trauma. Our data suggests that this might be due to an impairment of stem cell mobilization from the bone marrow in adults. Current investigations surround the use of animal models to corroborate human data that has already been procured.

• Laboratory of Michael P. Murphy, MD

  Dr. Murphy's research consortium includes four senior scientists (PhD), two technicians and three study coordinators housed in 1,100 square feet of space in the R3 (Walther Hall) and the Richard Roudebush VAMC. The lab also serves as the 3D Bioprinting Core for the VA Research faculty. Dr. Murphy's expertise is in developing novel therapeutic strategies for cardiovascular disease in the lab and rapidly translating these discoveries into first-in-man investigator-designed clinical trials. The lab collaborates with researchers at Harvard, MIT, and Stanford.

• Laboratory of Dr. Hari Nakshatri, PhD, General Surgery

  Dr. Nakshatri studies the molecular drivers of therapy resistance in breast cancer. His laboratory was the first to identify the role of the protein complex, NF-kappaB, which controls genes that respond to environmental stress and infection in triple negative breast cancer. He also identified biomarkers that may predict response to anti-estrogen therapy. Utilizing normal breast tissues of women of different ethnic background, his group has discovered genetic ancestry-dependent heterogeneity in the normal breasts, which has important implications on how tumors are characterized for genomic abnormalities. His recently published studies may provide insights into why hormone-responsive breast tumors are more common in women of European ancestry and why triple negative breast cancers are aggressive in women of African ancestry. Additionally, his group is mapping the normal breasts as well as the breasts of BRCA1/2 mutation careers at single cell resolution using single cell sequencing techniques. These efforts may lead to classification of breast cancer based on “cell-of-origin” of tumor. He is using systems biology approaches to understand organ specific breast cancer metastasis and developing patient-derived tumor models that reflect organ-specific metastasis and therapy resistance.

• Laboratory of Milan Radovich, PhD, General Surgery

  The Radovich laboratory focuses on the use of genomics in translational oncology. In particular, our research concentrates on the use of genomics for precision medicine, clinical trials, genomically-informed drug combinations, circulating biomarkers of cancer detection, companion diagnostics, and novel bioinformatic pipelines for cancer genome analyses. Our lab has long standing-expertise in the research of triple-negative breast cancer, thymic malignancies, and cancer precision medicine. In addition, Dr. Radovich leads the IU Health Precision Genomics Program, a clinical service line that uses cancer genomics to guide therapy for metastatic cancer patients. Research endeavors from this clinical program include: biomarkers of treatment response; understanding germline genetic variation and cancer predisposition; and genomically-directed clinical trials.

• Laboratory Sashwaty Roy, PhD, General Surgery

  Over the last 20 years, Dr. Roy's research has focused on the study of inflammation and diabetic wound healing. Her laboratory has been successful in setting up several innovative methodologies and models that are of high experimental/translational value. Upon extravasation, macrophages (mϕ) acquire functions in response to wound micro environmental cues. To understand role of mϕ in tissue repair and regeneration, it is therefore essential to study wound macrophage (wmϕ) in their natural milieu. As a part of her NIH RO1 award from NIDDK, her group pioneered the approach to isolate and study functionally intact macrophages from human chronic diabetic wounds and wound fluids presented at the wound clinics. We propose that wound macrophage plasticity is a major determinant of diabetic wound healing outcomes. We observed large-scale conversion of wound macrophages to fibroblasts at the wound site. More than one-half of the wound-site fibroblasts originate from myeloid cells. Wound macrophage plasticity is compromised in diabetic patients. We have demonstrated that miR-21 plays a major role in retaining macrophage plasticity and that the level of miR-21 is attenuated in diabetic wound macrophages.

• Laboratory of C. Max Schmidt, MD, PhD

  The Schmidt laboratory performs “bench-to-bedside” or translational research to discover novel biomarkers and targeted treatments for patients with pancreatic neoplasia. Our earlier work involved the use of multiple animal models to investigate the role of inflammatory pathways (i.e. cyclooxygenase-2 (COX-2), transcription factor nuclear factor-κB [NF-κB]) in pancreatic cancer and identify potential therapeutics. More recently, our research has focused on the discovery of biomarkers that can aid the early detection of pancreatic cancer as well as differentiate benign from potentially malignant pancreatic cysts. An invaluable resource available for these biomarker studies is the IU Pancreas Tissue Fluid Bank, established by Dr. Schmidt in 2001. Samples from >1500 patients with pancreatic disease are currently stored in the bank, including plasma/serum, bile, pancreatic cyst/duct fluid, urine and tissue. Additionally, longitudinal samples are being collected from patients “at risk” of pancreatic cancer at the IU Pancreatic Cancer and Cyst Early Detection Center (PCC-EDC, www.pancyst.org), directed by Dr. Schmidt. Ongoing global analyses include metabolomics/proteomics.

  Residents joining the laboratory have the opportunity to perform clinical outcomes research and translational research projects as outlined below. Residents submit abstracts for oral presentation at regional/national surgical meetings and publish their work in surgical or basic science journals.

• Laboratory of Chandan K. Sen, PhD

  The overriding theme that covers the research interests of the Sen Lab across programs is “Tissue Injury and Repair." This overarching umbrella includes regenerative medicine and cell-based therapies, stroke, tissue injury and repair, miRNA in injury and repair, cell and tissue reprogramming, redox signaling, wound healing, tissue oxygenation, wound epigenetics and biofilm infection. The Sen Lab studies how to tap into the power of regenerative medicine and engineering to heal burn wound, develop new therapies for diabetic complications, treat injured soldiers, and even regrow damaged and diseased tissue. Rather than starting with potentially renegade stem cells, researchers at Sen Lab turns pre-existing cells, such as skin cells, to another cell type such as a blood vessel or neuron cell. The research group works across a comprehensive platform covering basic cell culture, small and large animal models, human and patient-based research. Recently, the group has started transcriptional profiling of healthy uninjured skin and diabetic foot ulcer (DFU) tissue obtained from amputated limb skin through single-cell level mRNA-sequencing (scRNA-seq). Combined information obtained from diabetic wound tissue normalized to normal skin will help us create complex cellular networks that are altered by diabetes and impact vascular regeneration.

• Laboratory of Dimitrios Stefanidis, MD, PhD

  MIS/ Bariatric Research Fellowship

  This MIS/Bariatric Research Fellowship  in the MIS/ bariatric section of the Department of Surgery at Indiana University School of Medicine aims to provide a comprehensive clinical outcomes research experience in minimally invasive and bariatric surgery to a resident. Along with the research resident, the team includes a PhD psychologist, one data manager, a clinical fellow, a research nurse, an international research fellow, medical students, several MIS/ bariatric surgeons and other ad hoc members. The research resident obtains a Master's in biostatistics to enrich his/her research knowledge and skills, and engages in a number of clinical outcome research and process improvement projects. Their work is presented at a variety of surgical meetings and published in high impact surgical journals. This 2-year experience provides residents with the necessary skills, support and a nurturing environment that empowers them to excel in clinical research and become leaders in MIS bariatric surgery.

• Laboratory of Nicholas J. Zyromski, MD, Surgical Oncology

  Dr. Zyromski’s laboratory program was established in 2006 and has focused on basic, clinical and translational research related to pancreatic disease since its founding. The current focus of the laboratory is directed toward understanding the natural history of and developing treatments for patients with necrotizing pancreatitis. This focus involves both clinical and translational research. Dr. Zyromski has mentored 19 research residents since 2006.