Hollings Home  
 
Kevin F Staveley-O'Carroll, MD, PhD
Professor of Surgery
College of Medicine
MUSC

Email: staveley@musc.edu
 
       Print This Page
       
 
 


 

Kevin F Staveley-O'Carroll, MD, PhD

Return to Search Page  

Research Interest:

As a physician-scientist, one goal has been to translate my basic research into clinical practice.  My studies assessing the effects of opioid growth factor on the growth of hepatocellular cancer have led directly to an investigator-initiated Phase I clinical trial that is nearing completion. My studies of ceramide nanoliposomes’ in vivo inhibition of hepatocellular cancer (Gut, 2010, IF-10.6, featured in Nature Reviews) will be assessed in Phase I clinical trial pending FDA approval of the IND application. I also have clinical protocols assessing the changes in the immune-response to HCC antigens, AFP and GPC-3, which occur with radiofrequency ablation or chemoembolization in patients with hepatocellular cancer. My current project has been conceived with similar translational goals in mind and was funded by the NIH to elucidate the cellular and molecular mechanisms by which the chemotherapeutic agent sunitinib prevents immunotolerance and enhances T-cell mediated immunotherapy of hepatocellular cancer. I have established a unique murine model with the typical fibrosis/cirrhosis and hepatocellular cancer features seen in human hepatocellular cancer. My team has now demonstrated that tumor antigen-specific CD8 T-cell tolerance is prevented by the administration of sunitinib, an FDA approved inhibitor of multiple receptor tyrosine kinases. Moreover, we made the critical observation that sunitinib combined with adoptive transfer of CD8 T-cells leads to durable long term regression of established hepatocellular cancer tumors. These results suggest that sunitinib blocks the development of an immunosuppressive state within the liver, allowing effective immunotherapy. This study will advance our knowledge of the sunitinib-mediated mechanisms of action on distinct immune cell subsets in the setting of hepatocellular cancer. The knowledge gained will lay the foundation for translational approaches in human hepatocellular cancer that combines this chemotherapeutic drug with new or existing immunotherapies.

Honors:
Alice Ruth Reeves Folk Endowed Chair of Clinical Oncology

Positions:
Chief, Section of Surgical Oncology, Department of Surgery, Medical University of South Carolina
Medical Director, Hollings Cancer Center Clinical Service Line, Medical University of South Carolina
Director, Cell Evaluation & Therapy Shared Resource, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Findlay VJ, Wang C, Nogueira LM, Hurst K, Quirk D, Ethier SP, Staveley-O'Carroll KF, Watson DK, Camp ER. SNAI2 modulates colorectal cancer 5-fluorouracil sensitivity through miR145 repression. Mol Cancer Ther. ., 2014.
View in: PubMed

2.Kulaylat AN, Bhayani NH, Stokes AL, Schubart JR, Wong J, Kimchi ET, Staveley-O'Carroll KF, Kaifi JT, Gusani NJ. Determinants of Repeat Curative Intent Surgery in Colorectal Liver Metastasis. J Gastrointest Surg. ., 2014.
View in: PubMed

3.Jiang Y, Mackley HB, Kimchi ET, Zhu J, Gusani N, Kaifi J, Staveley-O'Carroll KF, Belani CP. Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer. Cancer Chemother Pharmacol. .74(1):205-10, 2014.
View in: PubMed

4.Yoo L, Oluyemi A, Dye C, Staveley-O'Carroll K, Mathew A. Removal of a partially prolapsing intraductal ampullar adenoma. Gastrointest Endosc. .79(3):377, 2014.
View in: PubMed

5.Nikfarjam M, Weinberg L, Fink MA, Muralidharan V, Starkey G, Jones R, Staveley-O'Carroll K, Christophi C. Pressurized pulse irrigation with saline reduces surgical-site infections following major hepatobiliary and pancreatic surgery: randomized controlled trial. World J Surg. .38(2):447-55, 2014.
View in: PubMed

6.Bhayani NH, Enomoto LM, James BC, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Multivisceral and extended resections during pancreatoduodenectomy increase morbidity and mortality. Surgery. .155(3):567-74, 2013.
View in: PubMed

7.Kline CL, Schiccitano A, Zhu J, Beachler C, Sheikh H, Harvey HA, Mackley HB, McKenna K, Staveley-O'Carroll K, Poritz L, Messaris E, Stewart D, Sivik J, El-Deiry WS. Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens. Clin Colorectal Cancer. .13(2):119-26, 2013.
View in: PubMed

8.Bhayani NH, Miller JL, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Perioperative outcomes of pancreaticoduodenectomy compared to total pancreatectomy for neoplasia. J Gastrointest Surg. .18(3):549-54, 2013.
View in: PubMed

9.Kaifi JT, Kunkel M, Zhu J, Dicker DT, Gusani N, Yang Z, Sarwani NE, Li G, Kimchi ET, Staveley-O'Carroll KF, El-Deiry WS. Circulating tumor cells are associated with diffuse spread in stage IV colorectal cancer patients. Cancer Biol Ther. .14(12):1174-81, 2013. PMCID: PMC3912041
View in: PubMed

10.Bhayani NH, Enomoto LM, Miller JL, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Morbidity of total pancreatectomy with islet cell auto-transplantation compared to total pancreatectomy alone. HPB (Oxford). .16(6):522-7, 2013. PMCID: PMC4048073
View in: PubMed

11.Kulaylat AN, Sahajwani S, Staveley-O'Carroll KF, Kaifi JT. Reconstructive options for gastroesophageal junction adenocarcinoma after Roux-en-Y gastric bypass. J Thorac Cardiovasc Surg. .146(5):1296-8, 2013.
View in: PubMed

12.Bhayani NH, Hamed OH, Gupta A, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Do patients' outcomes suffer when surgical fellows are involved in hepatic resection? Surgery. .154(5):1024-30, 2013.
View in: PubMed

13.Lim B, Scicchitano A, Beachler C, Gusani N, Sarwani N, Yang Z, Staveley-O'Carroll K, Ashkenazi A, Portera C, El-Deiry WS. FOLFIRI plus dulanermin (rhApo2L/TRAIL) in a patient with BRAF-mutant metastatic colon cancer. Cancer Biol Ther. .14(8):711-9, 2013. PMCID: PMC3841210
View in: PubMed

14.Kavuturu S, Sarwani NE, Ruggeiro FM, Deshaies I, Kimchi ET, Kaifi JT, Staveley-O'Carroll KF, Gusani NJ. Lymphoepithelial cysts of the pancreas. Can preoperative imaging distinguish this benign lesion from malignant or pre-malignant cystic pancreatic lesions? JOP. .14(3):250-5, 2013.
View in: PubMed

15.Hamed O, Kimchi ET, Sehmbey M, Gusani NJ, Kaifi JT, Staveley-O'Carroll K. Impact of genetic targets on cancer therapy: hepatocellular cancer. Adv Exp Med Biol. .779:67-90, 2013.
View in: PubMed

16.Hamed OH, Bhayani NH, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Simultaneous colorectal and hepatic procedures for colorectal cancer result in increased morbidity but equivalent mortality compared with colorectal or hepatic procedures alone: outcomes from the National Surgical Quality Improvement Program. HPB (Oxford). .15(9):695-702, 2012. PMCID: PMC3948537
View in: PubMed

17.Kaifi JT, Kibbe MR, Lemaire SA, Staveley-O'Carroll KF, Kao LS, Sosa JA, Kimchi ET, Pawlik TM, Gusani NJ. Scientific impact of Association for Academic Surgery and Society of University Surgeons plenary session abstracts increases in the era of the Academic Surgical Congress from 2006 to 2010. J Surg Res. .182(1):6-10, 2012.
View in: PubMed

18.Avella DM, Li G, Schell TD, Liu D, Zhang SS, Lou X, Berg A, Kimchi ET, Tagaram HR, Yang Q, Shereef S, Garcia LS, Kester M, Isom HC, Rountree CB, Staveley-O'Carroll KF. Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model. Hepatology. .55(1):141-52, 2012. PMCID: PMC3243781
View in: PubMed

19.Jiang Y, DiVittore NA, Kaiser JM, Shanmugavelandy SS, Fritz JL, Heakal Y, Tagaram HR, Cheng H, Cabot MC, Staveley-O'Carroll KF, Tran MA, Fox TE, Barth BM, Kester M. Combinatorial therapies improve the therapeutic efficacy of nanoliposomal ceramide for pancreatic cancer. Cancer Biol Ther. .12(7):574-85, 2011. PMCID: PMC3218384
View in: PubMed

20.Krishnegowda G, Prakasha Gowda AS, Tagaram HR, Carroll KF, Irby RB, Sharma AK, Amin S. Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway. Bioorg Med Chem. .19(20):6006-14, 2011. PMCID: PMC3235409
View in: PubMed

21.Avella DM, Podany A, Staveley-O'Carroll KF, Kaifi JT. Laparoscopic repair of post-esophagectomy diaphragmatic hernias using human acellular dermal matrix. Interact Cardiovasc Thorac Surg. .13(2):248-9, 2011.
View in: PubMed

22.Kaifi JT, Gusani NJ, Jiang Y, Mackley HB, Dye CE, Mathew A, Kimchi ET, Reed MF, Staveley-O'Carroll KF. Multidisciplinary management of early and locally advanced esophageal cancer. J Clin Gastroenterol. .45(5):391-9, 2011.
View in: PubMed

23.Tagaram HR, Divittore NA, Barth BM, Kaiser JM, Avella D, Kimchi ET, Jiang Y, Isom HC, Kester M, Staveley-O'Carroll KF. Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. Gut. .60(5):695-701, 2010.
View in: PubMed

24.Nikfarjam M, Kimchi ET, Gusani NJ, Staveley-O'Carroll KF. Complete surgical resection of giant mucinous hepatic cystadenomas. Am Surg. .76(5):E17-9, 2010.
View in: PubMed

25.Avella DM, Kimchi ET, Donahue RN, Tagaram HR, McLaughlin PJ, Zagon IS, Staveley-O'Carroll KF. The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer. Am J Physiol Regul Integr Comp Physiol. .298(2):R459-66, 2009. PMCID: PMC2828179
View in: PubMed

26.Kimchi ET, Nikfarjam M, Gusani NJ, Avella DM, Staveley-O'Carroll KF. Combined pancreaticoduodenectomy and extended right hemicolectomy: outcomes and indications. HPB (Oxford). .11(7):559-64, 2009. PMCID: PMC2785950
View in: PubMed

27.Avella D, Garcia LJ, Gusani NJ, Nikfarjam M, Shereef S, Kimchi ET, Staveley-O'Carroll KF. Human acellular dermal matrix: an innovative tool for diaphragmatic reconstruction in patients with large intra-abdominal tumors. Am J Surg. .199(1):e12-6, 2009.
View in: PubMed

28.Nikfarjam M, Kimchi ET, Gusani NJ, Shah SM, Sehmbey M, Shereef S, Staveley-O'Carroll KF. A reduction in delayed gastric emptying by classic pancreaticoduodenectomy with an antecolic gastrojejunal anastomosis and a retrogastric omental patch. J Gastrointest Surg. .13(9):1674-82, 2009.
View in: PubMed

29.Nikfarjam M, Kimchi ET, Gusani NJ, Avella DM, Shereef S, Staveley-O'Carroll KF. Reduction of surgical site infections by use of pulsatile lavage irrigation after prolonged intra-abdominal surgical procedures. Am J Surg. .198(3):381-6, 2009.
View in: PubMed

30.Nikfarjam M, Sehmbey M, Kimchi ET, Gusani NJ, Shereef S, Avella DM, Staveley-O'Carroll KF. Additional organ resection combined with pancreaticoduodenectomy does not increase postoperative morbidity and mortality. J Gastrointest Surg. .13(5):915-21, 2009.
View in: PubMed

31.Gusani NJ, Jiang Y, Kimchi ET, Staveley-O'Carroll KF, Cheng H, Ajani JA. New pharmacological developments in the treatment of hepatocellular cancer. Drugs. .69(18):2533-40, 2009.
View in: PubMed

32.Nikfarjam M, Shereef S, Kimchi ET, Gusani NJ, Jiang Y, Avella DM, Mahraj RP, Staveley-O'Carroll KF. Survival outcomes of patients with colorectal liver metastases following hepatic resection or ablation in the era of effective chemotherapy. Ann Surg Oncol. .16(7):1860-7, 2008.
View in: PubMed

33.Ryan CM, Staveley-O'Carroll K, Schell TD. Combined anti-CD40 conditioning and well-timed immunization prolongs CD8+ T cell accumulation and control of established brain tumors. J Immunother. .31(9):906-20, 2008. PMCID: PMC2923041
View in: PubMed

34.Garcia LJ, Avella DM, Hartman B, Kimchi E, Staveley-O'Carroll KF. Thoracoabdominal incision: a forgotten tool in the management of complex upper gastrointestinal complications. Am J Surg. .197(2):e28-31, 2008.
View in: PubMed

35.Avella D, Garcia L, Hartman B, Kimchi E, Staveley-O'Carroll K. Esophageal extension encountered during transhiatal resection of gastric or gastroesophageal tumors: attaining a negative margin. J Gastrointest Surg. .13(2):368-73, 2008.
View in: PubMed

36.Nikfarjam M, Kimchi E, Shereef S, Gusani NJ, Jiang Y, Liang J, Sehmbey M, Staveley-O'Carroll KF. Surgical outcomes of patients with gastrointestinal stromal tumors in the era of targeted drug therapy. J Gastrointest Surg. .12(11):2023-31, 2008.
View in: PubMed

37.Tagaram HR, Watson AM, Lemonnier FA, Staveley-O'Carroll K, Tevethia SS, Schell TD. An SV40 VP1-derived epitope recognized by CD8+ T cells is naturally processed and presented by HLA-A*0201 and cross-reactive with human polyomavirus determinants. Virology. .376(1):183-90, 2008. PMCID: PMC2464359
View in: PubMed

38.Choudry H, Avella D, Garcia L, Han D, Staveley-O'Carroll K, Kimchi E. Use of the left renal vein as a practical conduit in superior mesenteric vein reconstruction. J Surg Res. .146(1):117-20, 2007.
View in: PubMed

39.Staveley-O'Carroll K, Schell TD, Jimenez M, Mylin LM, Tevethia MJ, Schoenberger SP, Tevethia SS. In vivo ligation of CD40 enhances priming against the endogenous tumor antigen and promotes CD8+ T cell effector function in SV40 T antigen transgenic mice. J Immunol. .171(2):697-707, 2003.
View in: PubMed

40.Sotomayor EM, Borrello I, Rattis FM, Cuenca AG, Abrams J, Staveley-O'Carroll K, Levitsky HI. Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood. .98(4):1070-7, 2001.
View in: PubMed

41.Staveley-O'Carroll K, Sotomayor E, Montgomery J, Borrello I, Hwang L, Fein S, Pardoll D, Levitsky H. Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acad Sci U S A. .95(3):1178-83, 1998. PMCID: PMC18712
View in: PubMed