Surgical Oncology Research

Our research group is interested in improving clinical outcomes and healthcare delivery in patients with gastrointestinal and HPB pathology including both malignant and non-malignant diseases. Specific projects focus on improving patient selection, treatment decision-making, access to care, as well as short- and long-term patient specific outcomes.

To address large scale patient decision making and outcome questions we frequently use population level database tools, such as National Inpatient Sample (NIS), National Surgical Quality Improvement Program (NSQIP), Surveillance of Epidemiology and End Results (SEER), and Virginia Cancer Registry (VCR).

When sufficient data granularity cannot be achieved with variable collected in large population-level datasets, we either use available merged databases, such as SEER-Medicare, or create our own merged datasets by combining NSQIP data with institutional patient populations or combining NSQIP with UVA Cancer Center Registry data. We also employ complex decision analysis methods to address equipoise in comparative effectiveness treatment questions that cannot be sufficiently answered using retrospective cohort or case-control study designs.

Current projects aim to examine long term outcomes in geriatric patients selected for major gastrointestinal and hepato-pancreatobiliary operations with a plan to integrate pre- and post-operative patient related outcomes metrics. In addition, we are studying patient-specific disparities in survival and access to care among populations of GI/HPB cancer patients treated at UVA Cancer Center.

The primary focus of the Bauer laboratory is to determine the drivers of tumor growth and metastasis in pancreatic cancer and colorectal cancer in order to identify novel approaches to therapy.

The Bauer laboratory has developed a human pancreatic cancer tissue bank and human colorectal cancer tissue bank with extensive genetic and molecular characterization of the tumors and mouse PDX models of primary and metastatic disease. Using these low-passage human tumors and mouse xenograft models, we have investigated the tumor cells and the tumor microenvironment to determine the key drivers of tumor growth and metastasis, then tested novel therapies. We believe that collaboration and team science are the keys to success.

Publications:

1. Walters DM, Stokes JB, Adair SJ, Stelow EB, Borgman CA, Lowrey BT, Xin W, Blais EM, Lee JK, Papin JA, Parsons JT, Bauer TW. Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens. PLOS ONE, 8(10):e77065, 2013. PMCID: PMC3799939.
2. Newhook TE, Blais EM, Lindberg JM, Adair SJ, Xin W, Lee JK, Papin JA, Parsons JT, Bauer TW. A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. PLOS ONE  Sep;9(9):e105631, 2014. PMCID: PMC4152146.
3. Gioeli D, Snow CJ, Simmers MB, Hoang SA, Figler RA, Allende JA, Roller DG, Parsons JT, Wulfkuhle JD, Petricoin EF, Bauer TW, Wamhoff BR. Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells. Lab Chip Mar 27;19(7):1193-1204, 2019.
4. Nagdas S, Kashatus JA, Nascimento A, Hussain SS, Trainor RE, Pollock SR, Adair SJ, Michaels AD, Sesaki H, Stelow EB, Bauer TW, Kashatus DF. Drp1 promotes Kras-driven metabolic changes to drive pancreatic tumor growth. Cell Rep, 2019 Aug 13;28(7):1845-59. PMCID: PMC6711191.
5. Walters DM, Lindberg J, Adair SJ, Newhook TE, Cowan CR, Stokes JB, Borgman CA, Stelow EB, Lowrey BT, Chopivsky ME, Gilmer TM, Parsons JT, Bauer TW. Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib. Neoplasia, 15(2):143-55, 2012. PMCID: PMC3579317.
6. Lindberg, JM, Newhook TE, Adair SJ, Walters DM, Kim AJ, Stelow EB, Parsons JT, Bauer TW. Co-treatment with panitumumab and trastuzumab augments response to the MEK inhibitor trametinib in a patient-derived xenograft model of pancreatic cancer. Neoplasia Jul;16(7):562-71, 2014. PMCID: PMC4198828.
7. Szlachta K, Kuscu C, Tufan T, Adair SJ, Shang S, Michaels AD, Mullen MG, Fischer NL, Yang J, Liu L, Trivedi P, Stelow EB, Stukenberg PT, Parsons JT, Bauer TW, Adli M. CRISPR knockout screening identifies combinatorial drug targets in pancreatic cancer and models cellular drug response. Nat Commun, Oct 15;9(1):4275, 2018. PMCID: PMC6189038.
8. Wei X, Yang J, Adair SJ, Ozturk H, Kuscu C, Lee KY, Kane WJ, O’Hara PE, Liu D, Demirlenk YM, Habieb AH, Yilmaz E, Dutta A, Bauer TW, Adli M. Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells. Proc Natl Acad Sci USA, Nov 10;117(45):28068-79, 2020. PMID: 33097661.
9. Newhook TE, Lindberg JM, Adair SJ, Kim AJ, Stelow EB, Rahma OE, Parsons JT, Bauer TW. Adjuvant trametinib delays the outgrowth of pancreatic cancer in a mouse model of patient-derived liver metastasis. Ann Surg Oncol 2016 Jun;23(6):1993-2000. PMCID: PMC5637098.
10. Michaels AD, Newhook TE, Adair SJ, Morioka S, Goudreau BJ, Nagdas S, Mullen MG, Persily JB, Bullock T, Slingluff CL, Ravichandran KS, Parsons JT, Bauer TW. CD47 blockade as an adjuvant immunotherapy for resectable pancreatic cancer. Clin Cancer Res 2018 Mar 156;24(6):1415-1425. PMCID: PMC6296745.
11. Bausch D, Thomas S, Mino-Kenudson M, Fernandez-del Castillo C, Bauer TW, Williams M, Warshaw AL, Thayer SP, Kelly KA. Plectin-1 as a novel biomarker for pancreatic cancer. Clinical Cancer Research. Jan 15; 17(2):302-9, 2011. PMCID: PMC3044444.
12. Honrado C, Salahi A, Adair SJ, Moore JH, Bauer TW, Swami NS. Automated biophysical classification of apoptotic pancreatic cancer cell subpopulations by using machine learning approaches with impedance cytometry. Lab Chip 2022 Aug 23. Online ahead of print. PMID: 35997278.

The Translational Oncology and Therapeutics Research lab has a long-standing record of examining the role of innate immunity in injury-induced inflammation and tumorigenesis of primary and metastatic liver cancer, with particular expertise in neutrophil and macrophage biology, damage-associated molecular pattern (DAMP) danger responses, autophagy and mitochondrial function, using clinically relevant models of injury and cancer. By employing diverse strategies, we have contributed substantially to understanding the cellular and molecular biology of acute and chronic inflammatory states as well as the tumor microenvironment. The strong translational perspective of our investigations, which capitalize upon analyses of human cohort data and clinical correlates of our animal-based studies, has enabled us to provide mechanistic insight into the clinically relevant outcomes of organ dysfunction and cancer progression via tumor cell survival, expansion, and metastases.

Our lab has an extensive experience in biochemistry and molecular biology research, and our overarching research direction revolves around the understanding of the role of the tumor microenvironment in various oncologic disease processes, and providing novel strategy for prevention and cure, especially the role of hepatic immune responses after pre-operative exercise therapy. Our other research interests include innate immune and inflammatory responses in liver sterile injury, and innate immunity in development of hepatocellular carcinoma.

Publications:

http://www.ncbi.nlm.nih.gov/pubmed/?term=tsung+a

1. Wang H, Zhang H, Wang Y, Brown ZJ, Xia Y, Huang Z, Shen C, Hu Z, Beane J, Ansa-Addo EA, Huang H, Tian D, Tsung A. Regulatory T cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis. J Hepatol. 2021 Aug 4:S0168-8278(21)01962-0. doi: 10.1016/j.jhep.2021.07.032. PMID: 34363921
2. Zhang H, Chen T, Ren J, Xia Y, Onuma A, Wang Y, He J, Wu J, Wang H, Hamad A, Shen C, Zhang J, Asara JM, Behbehani GK, Wen H, Deng M, Tsung A, Huang H. Pre-operative exercise therapy triggers anti-inflammatory trained immunity of Kupffer cells through metabolic reprogramming. Nature Metab. 2021 Jun;3(6):843-858. doi: 10.1038/s42255-021-00402-x. PMID: 34127858 (Co-Senior Author)
3. Ren J, He J, Zhang H, Xia Y, Hu Z, Loughran P, Billiar T, Huang H, Tsung A. Platelet TLR4-ERK5 Axis Facilitates NET-Mediated Capturing of Circulating Tumor Cells and Distant Metastasis after Surgical Stress. Cancer Res. 2021 Mar 9. doi: 10.1158/0008-5472.CAN-20-3222. PMID: 33687949
4. van der Windt DJ, Sud V, Zhang H, Varley PR, Goswami J, Yazdani HO, Tohme S, Loughran P, O’Doherty RM, Minervini MI, Huang H, Simmons RL, Tsung A. Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in non-alcoholic steatohepatitis. Hepatology. 2018; 68(4):1347-1360.
5. Yazdani HO, Chen HW, Tohme S, Tai S, van der Windt DJ, Loughran P, Rosborough BR, Sud V, Beer-Stolz D, Turnquist HR, Tsung A, Huang H. IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation. J Hepatol. 2017. [Epub ahead of print]
6. Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Lougharn P, Mowen K, Wang Y, Simmons RL, Huang H, Tsung A. Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases after Surgical Stress. Cancer Res. 2016; 76(6):1367-80.
7. Huang H, Tohme S, Al-Khafaji AB, Tai S, Loughran P, Chen L, Wang S, Kim J, Billiar T, Wang Y, Tsung A. DAMPs-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury. Hepatology. 2015; 62(2):600-14.
8. Huang H, Nace GW, McDonald KA, Tai S, Klune JR, Rosborough BR, Ding Q, Loughran P, Zhu X, Beer-Stolz D, Chang EB, Billiar T, Tsung A. Hepatocyte specific HMGB1 deletion worsens the injury in liver ischemia/reperfusion: A role for intracellular HMGB1 in cellular protection. Hepatology. 2014; 59(5): 1984-97.
9. Nace GW, Huang H, Klune JR, Eid RE, Rosborough BR, Korff S, Li S, Shapiro RA, Stolz DB, Sodhi CP, Hackam DJ, Geller DA, Billiar TR, Tsung A. Cellular specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury. Hepatology. 2013; 58(1):374-87.
10. Chang Y, Yan W, He X, Zhang L, Li C, Huang H, Nace G, Geller DA, Lin J, Tsung A. miR-375 Inhibits Autophagy and Reduces Viability of Hepatocellular Carcinoma Cells Under Hypoxic Conditions. Gastroenterology. 2012; 143(1):177-187.
11. Cardinal J, Pan P, Tsung A. Protective role of cisplatin in ischemic liver injury through induction of autophagy. Autophagy. 2009; 5(8):1211-2.
12. Tsung A, Klune JR, Zhang X, Jeyabalan G, Cao Z, Peng X, Stolz DB, Geller DA, Rosengart MR, Billiar TR. Ischemia-induced HMGB1 Release by Hepatocytes Involves Toll-like Receptor 4 Dependent Reactive Oxygen Species Production and Calcium Mediated Signaling. J Exp Med. 2007; 204(12):2913-23.
13. Tsung A, Sahai R, Tanak H, Nakao A, Fink MP, Lotze MT, Yang H, Li J, Tracey KJ, Geller Da, Billiar TR. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med. 2005; 205:1-10.