Jennifer Carew, PhD

Associate Professor, Medicine
Co-Director, Hematologic Malignancy Disease Team
Email Address: 
Phone Number: 
(520) 626-2272

Clinical Information

Laboratory/Office: 

Research Information

Research Program: 
Therapeutic Development
Member Status: 
Research Member
Year of Membership Acceptance: 
2016
Research Focus: 
  • Translational cancer researcher with expertise in experimental cancer therapeutics, mechanisms of cell death and drug resistance, in vitro and in vivo preclinical investigation of developmental cancer therapeutics, Phase I clinical trial design, and clinical trial correlates
  • 15 years of research experience in basic and translational hematology and oncology
  • 6 years of experience as the Co-Director of a contract research organization laboratory evaluating the preclinical activity and mechanism of action of novel cancer therapeutics in cell lines, primary patient specimens, and mouse models of cancer
  • Track record of strong industry collaborations focused on investigational drugs, strategies to translate preclinical findings into clinical trials, and development of rational correlative studies in support of clinical trials
  • Patent inventor of novel anticancer agents
Selected Publications: 
  1. Kelly KR, Espitia CM, Zhao W, Wendlandt E, Tricot G, Zhan F, Carew JS, and Nawrocki ST. Junctional adhesion molecule-A is overexpressed in advanced multiple myeloma and determines response to reolysin. (submitted)
  2. Nazha A, Seastone D, Radivoyevitch T, Dienes B, Przychodzen B, Carraway H, Patel B, Carew J, Makishima H, Sekeres M, Maciejewski JP. Genomic patterns associated with hyoplastic compared to hyper/normoblastic myelodyspladtic syndromes. (2015) Haematologica (in press)
  3. Carew JS, Espitia CM, Zhao W, Mita MM, Mita AC, and Nawrocki ST. Targeting survivin inhibits renal cell carcinoma progression and enhances the activity of temsirolimus. (2015) Mol Cancer Ther (in press)
  4. Nawrocki ST, Kelly KR, Smith PG, Keaton M, Carraway H, Sekeres M, Maciejewski J, and Carew JS. The NEDD8-activating enzyme inhibitor MLN4924 disrupts nucleotide metabolism and augments the efficacy of cytarabine. (2015) Clin Cancer Res 21:439-47.
  5. Mahalingam D, Mita M, Sarantopoulos J, Wood L, Amaravadi R, Davis L, Mita A, Curiel TJ, Nawrocki ST, Giles FJ, and Carew JS. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic and pharmacodynamic analysis of hydroxychloroquine in  combination with the HDAC inhibitor vorinostat in patients with solid tumors. (2014) Autophagy 10:1403-1414.
  6. Bansal H, Yihua Q, Iyer SP, Ganapathy S, Proia D, Penalva LO, Uren PJ, Suresh U, Carew JS, Larnad AB, Weitman S, Tomlinson GE, Rao M, Kornblau SM, and Bansal S. WTAP is a novel oncogenic protein Carew 5 in acute myeloid leukemia. (2014) Leukemia 28:1171-4.
  7. Carew JS, Espitia CM, Zhao W, Kelly KR, Coffey M, Freeman JW, and Nawrocki ST. Reolysin: A novel reovirus-based agent that induces endoplasmic reticular stress in RAS-activated pancreatic cancer. Cell Death Dis 4:e728.
  8. Nawrocki ST, Kelly KR, Smith PG, Espitia CM, Possemato A, Beausoleil SA, Milhollen MA, Blakemore S, Thomas M, Berger AJ, and Carew JS. Disrupting protein NEDDylation with MLN4924 is a novel strategy to target cisplatin resistance in ovarian cancer. (2013) Clin Cancer Res 19:3577-90.
  9. Carew JS, Kelly KR, and Nawrocki ST. Autophagy as a target for cancer therapy: new developments. (2012) Cancer Manag Res 4:357-65.
  10. Abraham J, Chua YX, Glover JM, Tyner JW, Loriaux MM, Kilcoyne A, Nelson LD, Carew JS, Pal R, Rivera VM, Druker BJ, Rubin BP, and Keller C. An adaptive Srd-PDGFRa-Raf axis in rhabdomyosarcoma. (2012) Biochem Biophys Res Commun 426:363-8.
  11. Nawrocki ST, Griffin P, Kelly KR, and Carew JS. MLN4924: a novel first-in-class inhibitor of NEDD8-activating enzyme for cancer therapy. (2012) Expert Opin Investig Drugs 21:1563-73.
  12. Kelly KR, Nawrocki ST, Espitia CM, Zhang M, Yang JJ, Padmanabhan S, Ecsedy J, Giles FJ, and Carew JS. Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism. (2012) Int J Cancer 131:2693-703.
  13. Rickles RJ, Tam WF, Giordano 3rd TP, Pierce LT, Farwell M, McMillin DW, Necheva A, Crowe D, Chen M, Avery W, Kansra V, Nawrocki ST, Carew JS, Giles FJ, Mitsiades CS, Borisy AA, Anderson KC, and Lee MS. Adenosine A2A and Beta-2 adrenergic receptor agonists: Novel selective and synergistic multiple myeloma targets discovered through systematic combination screening. (2012) Mol Cancer Ther 11:1432-42.
  14. Carew JS, Esquivel II JA, Espitia CM, Schultes CM, Mulbaier M, Lewis JD, Janssen B, Giles FJ, and Nawrocki ST. ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma. (2012) PLoS ONE 7:e31120.
  15. Klionsky DJ…Carew JS…Zuckerbraun B. Guidelines for the use and interpretation of assays monitoring autophagy. (2012) Autophagy 8:445-54.
  16. Kelly KR, Espitia CM, Taverna P, Choy G, Padmanabhan S, Nawrocki ST, Giles FJ, Carew JS. Targeting PIM kinase activity significantly augments the efficacy of cytarabine. (2012) Br J Haematol 156:129-32.
  17. Kelly KR, Espitia CM, Mahalingam D, Oyajobi BO, Coffey M, Giles FJ, Carew JS, Nawrocki ST. Reovirus therapy stimulates endoplasmic reticular stress, NOXA induction, and augments bortezomib-mediated apoptosis in multiple myeloma. (2012) Oncogene 31:3023-38.
  18. Kelly KR, Ecsedy J, Mahalingam D, Nawrocki ST, Padmanabhan S, Giles FJ, Carew JS. Targeting aurora kinases in cancer treatment. (2011) Current Drug Targets 12:2067-78.
  19. Swords R, Kelly K, Carew J, Nawrocki S, Mahalingam D, Sarantopoulos J, Bearss D, Giles F. The PIM kinases: new targets for drug development. (2011) Curr Drug Targets 12:2059-66.
  20. Mahalingam D, Espitia CM, Medina EC, Esquivel II JA, Kelly KR, Bearss D, Gavin C, Taverna P, Carew JS, Giles FJ, and Nawrocki ST. The novel PIM kinase inhibitor SGI-1776 significantly enhances the activity of sunitinib in renal cell carcinoma. (2011) Br J Cancer 105:1563-73.
  21. Kelly KR, Rowe JH, Padmanabhan S, Nawrocki ST, Carew JS. Mammalian target of rapamycim as a Carew 6 target in hematological malignancies. (2011) Target Oncol 6:53-61.
  22. Carew JS, Kelly KR, Nawrocki ST. Mechanisms of mTOR inhibitor resistance in cancer therapy. (2011) Target Oncol 6:17-27.
  23. Carew JS, Espitia C, Esquivel J, Mahalingam D, Kelly KR, Reddy G, Giles FJ, Nawrocki ST. Lucanthone: a novel inhibitor of autophagy. (2011) J Biol Chem 286:6602-13.
  24. Kelly KR, Ecsedy J, Medina E, Oberheu K, Mahalingam D, Nawrocki ST, Giles FJ, Carew JS. The novel aurora a kinase inhibitor MLN8237 is active in resistant chronic myeloid leukemia and significantly increases the efficacy of nilotinib. (2011) J Cell Mol Med 15:2057-70.
  25. Swords RT, Kelly KR, Smith PG, Garnsey JJ, Mahalingam D, Medina E, Oberheu K, Padmanabhan S, O'Dwyer M, Nawrocki ST, Giles FJ, Carew JS. Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. (2010) Blood 115:3796-800.
  26. Mahalingam D, Medina EC, Esquivel JA 2nd, Espitia CM, Smith S, Oberheu K, Swords R, Kelly KR, Mita MM, Mita AC, Carew JS, Giles FJ, Nawrocki ST. Vorinostat enhances the activity of temsirolimus in renal cell carcinoma through suppression of survivin levels. (2010) Clin Cancer Res 16:141-53.
  27. Swords R, Mahalingam D, O'Dwyer M, Santocanale C, Kelly K, Carew J, Giles F. Cdc7 kinase - a new target for drug development. (2010) Eur J Cancer 46:33-40.
  28. Carew JS, Medina E, Esquivel J, Mahalingam D, Swords R, Kelly K, Zhang H, Huang P, Mita AC, Mita MM, Giles FJ, and Nawrocki ST. Inhibition of autophagy stimulates ubiquitin-conjugated protein accumulation and enhances vorinostat-mediated apoptosis. (2010) J Cell Mol Med 14:2448-59.
  29. Swords R, Mahalingam D, Padmanabhan S, Carew J, Giles F. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib. (2009) Drug Des Devel Ther 3:89-101.
  30. Mahalingam D, Kelly KR, Swords RT, Carew J, Nawrocki ST, Giles FJ. Emerging drugs in the treatment of pancreatic cancer. (2009) Expert Opin Emerg Drugs 14:311-28.
  31. Mahalingam D, Swords R, Carew JS, Nawrocki ST, Bhalla K, Giles FJ. Targeting HSP90 for cancer therapy. (2009) Br J Cancer 100:1523-1529.
  32. Nawrocki ST*, Carew JS*, Maclean KH, Huang P, Houghton JA, Cleveland JL, Giles FJ and McConkey DJ. Myc regulates aggresome formation, noxa induction, and apoptosis induced by the combination of bortezomib and SAHA. (2008) Blood 112:2917-2926. *these authors contributed equally
  33. Carew JS, Giles FJ and Nawrocki ST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy (2008) Cancer Lett 269:7-17.
  34. Carew JS, Nawrocki ST, Giles FJ and Cleveland JL. Targeting autophagy: a novel anticancer strategy with therapeutic implications for imatinib resistance. (2008) Biologics: Targets and Therapy 2:201-204.
  35. Carew JS, Nawrocki ST, Reddy VK, Bush D, Rehg JE, Goodwin A, Houghton JA, Casero RA Jr, Marton LJ, and Cleveland JL. The novel polyamine analog CGC-11093 enhances the in vitro and in vivo antimyeloma activity of the proteasome inhibitor bortezomib. (2008) Cancer Res 68:4783-4790.
  36. Zhang H, Trachootham D, Lu W, Carew JS, Giles FJ, Keating MJ and Huang P. Effective killing of gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism. (2008) Leukemia 6:1191-1199.
  37. Carew JS, Nawrocki ST and Cleveland JL. Modulating autophagy for therapeutic benefit. (2007) Autophagy 3:464-467.
  38. Nawrocki ST, Carew JS, Douglas L, Cleveland JL, Humphreys R and Houghton JA. Histone deacetylase inhibitors enhance lexatumumab-induced apoptosis via a p21-dependent decrease in survivin levels. (2007) Cancer Res 67:6987-6994.
  39. Carew JS, Nawrocki ST, Kahue C, Zhang H, Yang C, Chung L, Houghton JA, Huang P, Giles FJ and Cleveland JL. Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl mediated drug resistance. (2007) Blood 110:313-322.
  40. Pelicano H, Xu RH, Du, M, Feng L, Sasaki R, Carew JS, Hu Y, Ramdas L, Hu L, Keating MJ, Zhang W, Plunkett W and Huang P. Mitochondrial respiration defects in cancer cells cause activation of akt survival pathway through a redox-mediated mechanism. (2006) J Cell Biol 176:913-923.
  41. Carew JS, Zhou Y and Huang P. Oxidative stress, cell proliferation, and apoptosis. In: Oxidative Stress, Disease and Cancer. Keshav, K. Singh, Ed. Chapter 9, Imperial College Press, London, UK, p. 309-332, 2006.
  42. Nawrocki ST, Carew JS, Pino MS, Highshaw RA, Andtbacka RHI, Dunner K Jr, Pal A, Bornmann WG, Chiao PJ, Huang P, Xiong H, Abbruzzese JL and McConkey DJ. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. (2006) Cancer Res 66:3773-3781.
  43. Pelicano H, Carew JS, McQueen TJ, Andreeff M, Plunkett W, Keating MJ and Huang P. Targeting Hsp90 by 17-AAG in leukemia cells: mechanisms for synergistic and antagonistic drug combinations with arsenic trioxide and ara-c. (2006) Leukemia 20:610-619.
  44. Carew JS, Nawrocki ST, Krupnik YV, Dunner K Jr., McConkey DJ, Keating MJ and Huang P. Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL. (2006) Blood 107:222-231.
  45. Nawrocki ST, Carew JS, Pino MS, Highshaw RA, Dunner K Jr, Huang P, Abbruzzese JL and McConkey DJ. Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. (2005) Cancer Res 65:11658-11666.
  46. Nawrocki ST, Carew JS, Dunner K Jr, Boise LH, Chiao PJ, Huang P, Abbruzzese JL and McConkey DJ. Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells. (2005) Cancer Res 65:11510-11519.
  47. Achanta G, Sasaki R, Feng L, Carew JS, Lu W, Pelicano H, Keating MJ and Huang P. Novel role of p53 in maintaining mitochondrial genetic instability through interaction with DNA Pol gamma. (2005) EMBO J 24:3482-3492.
  48. Choi W, Gerner EW, Ramdas L, Dupart J, Carew J, Proctor L, Huang P, Zhang W and Hamilton SR. Combination of 5-fluorouracil and N1,N11-diethylnorspermine markedly activates spermidine/spermine N1-acetyltransferase expression, depletes polyamines, and synergistically induces apoptosis in colon carcinoma cells. (2005) J Biol Chem 280:3295-3304.
  49. Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ and Huang P. Novel strategy to kill cancer cells with mitochondrial respiratory defects: therapeutic implications of the Warburg effect. (2005) Cancer Res 65:613-621.
  50. Carew JS, Nawrocki ST, Dunner K Jr., McConkey DJ, Wierda WG, Keating MJ and Huang P. Increased mitochondrial biogenesis in primary leukemia cells: the role of endogenous nitric oxide and impact on Carew 8 fludarabine sensitivity. (2004) Leukemia 18:1934-1940.
  51. MacEwen EG, Kutzke J, Carew J, Pastor J, Schmidt JA, Tsan R, Thamm DH and Radinsky R. c-mettyrosine kinase receptor expression and function in human and canine osteosarcoma cells. (2003) Clin Exp Metastasis 20:421-30.
  52. Pelicano H, Feng L, Zhou Y, Carew JS, Hileman EO, Plunkett W, Keating MJ and Huang P. Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in cancer cells by an ROSmediated mechanism. (2003) J Biol Chem 278:37832-39.
  53. Carew JS, Zhou Y, Albitar M, Keating MJ and Huang P. Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications. (2003) Leukemia 17:1437-47.
  54. Carew JS and Huang P. Mitochondrial defects in cancer. (2002) Molecular Cancer 1:9.

Professional Information

Positions and Honors: 
  • Leukemia and Lymphoma Society Scholar, 2012
  • Voelcker Fund Young Investigator Award, 2012
  • Leukemia Texas Young Investigator Award, 2008
  • American Cancer Society Postdoctoral Research Award, 2007
  • Sowell-Huggins Endowed Scholarship for Cancer Research, 2005
  • University of Texas Health Science Center and M.D. Anderson Cancer Center Presidents’ Research
  • Scholarship, 2005
  • American Legion Auxiliary Fellowship for Cancer Research, 2003-2005
  • Shell Oil Foundation Scholarship for Excellence in Toxicology Research, 2003
  • Edward S. Reynolds Award for Best Platform Presentation, Gulf Coast Society of Toxicology Annual
  • Meeting, 2003
  • Gulf Coast Society of Toxicology Travel Award, 2003
  • Society of Toxicology Travel Award, 2003
Other Experience and Professional Memberships/Affiliations: 
PATENTS
US Patent #8,524,762 B2 – Thioxanthone-based autophagy inhibitor therapies to treat cancer
US Patent Filed 07/2014 – Novel autophagy inhibitors for cancer therapy
 
AFFILIATIONS
American Association for Cancer Research
American Society of Hematology
European Hematology Association

Academic Information

Doctorate: 
Biomedical Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Tx
Undergraduate School: 
BS, Zoology, University of Wisconsin – Madison