TTUHSC School of Medicine
Cell Biology & Biochemistry

Patrick Reynolds, M.D. Ph.D.

Professor patrick.reynolds@ttuhsc.edu

Research Interests

Developmental therapeutics of adult and pediatric cancers in both laboratory and clinical studies. Types of drugs studied include retinoids, "vitamin A derivatives" as tumor-selective differentiation or cytotoxic agents and drugs such as depletors of glutathione or Bcl-2 inhibitors that overcome resistance to traditional cytotoxic agents. Other research identifies molecular mechanisms of drug resistance that may provide novel therapeutic targets in childhood and adult cancers, development of novel preclinical testing models for childhood and adult cancer drug development, and clinical trials testing novel therapeutic approaches for cancer.

To learn more, visit:

TTUHSC Cancer Center http://Cancer.TTUHSC.edu
Children’s Oncology Group (COG) Cell Line and Xenograft Repository: www.COGcell.org
NCI PPTP In Vitro Drug Testing Lab www.PPTPinvitro.org
COG Ewing’s Family Tumors Preclinical Testing Lab www.EFTlab.org
South Plains Oncology Consortium www.SPONC.org
Texas Cancer Cell Repository www.TXCCR.org
DrugPath Drug to Molecular Pathway matching database www.DrugPath.org

History & Education

Degrees

1974 BA Biology - University of Texas at Austin
1979 MD University of Texas Southwestern Medical School, Dallas, TX
1979 PhD Cell Biology - University of Texas at Austin

Postdoctoral Research Fellowships

1980 University of Texas Southwestern Medical School, Dallas, TX

Residency

1981 Pediatrics, National Naval Medical Center, Bethesda, Maryland

Honors

1988 Gold Medal for Research Achievement awarded by Nihon University, Tokyo, Japan
1992 Team Physician, 1992 USA Olympic Shooting Team, 25th Olympiad, Barcelona, Spain
2004 Eurand Prize for Novel Approaches in Oral Drug Delivery by the Controlled Release Society
2008 Best Clinical Paper Award, Advances in Neuroblastoma Research, Chiba, Japan
2011 Most cited paper in Clinical Cancer Research, 2009
(Clinical Cancer Research 15:1126-1132, 2009)

National and State Leadership and Advisory Positions

2000 - Present US FDA Pediatric Subcommittee of the Oncologic Drugs Advisory Committee
2007 - 2008 Natl. Cancer Inst. SBIR/STTR ZRG1 Cancer Drug Dev. + Therapeutics Study Section
2008 - Present Natl. Inst. Child Health and Development, Best Pharmaceuticals for Children Act Panel
2008 - Present Chartered member, Natl. Cancer Inst Drug Discovery + Molecular Pharm. Study Section
2009 - Present Advisory Committee on Childhood Cancer, Cancer Prevention Research Inst of Texas
2010 - Present Council of Principal Investigators, Texas Cancer Clinical Trials Network

Selected Peer-reviewed Publications

(selected from 154 peer-reviewed publication)

  1. Reynolds CP, Biedler JL, Spengler BA, Reynolds DA, Ross RA, Frenkel EP, Smith RG. Characterization of human neuroblastoma cell lines established before and after therapy. J National Cancer Institute 76:375 387, 1986.
  2. Wada RK, Seeger RC, Brodeur GM, Rayner SA, Tomayko MM, Reynolds CP: N-myc expression in human neuroblastoma cell lines without N-myc gene amplification, Cancer 72:3346-3354, 1993.
  3. Villablanca JG, Avramis V, Khan A, Matthay KK, Ramsay NKC, Seeger RC, Reynolds CP: Phase I trial of 13-cis-retinoic acid (cRA) in neuroblastoma patients following bone marrow transplantation (BMT). J Clinical Oncology 13:894-901, 1995.
  4. Keshelava N, Seeger RC, Groshen S, Reynolds CP: Drug resistance patterns of human neuroblastoma cell lines derived from patients at different phases of therapy. Cancer Research 58:5396-5405, 1998.
  5. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shamada H, Black CG, Brodeur GM, Gerbing R, Reynolds CP: Treatment of high risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. New England J Medicine 341:1165-1173, 1999.
  6. Maurer BJ, Cabot MC, Reynolds CP: Synergistic cytotxicity in solid tumor cell lines of N-(4-hydroxypheynl)- retinamide and modulators of ceramide metabolism. J National Cancer Institute 92:1897-1908, 2000.
  7. Keshelava N, Zuo JJ, Chen P, Waidyaratine SN, Luna MC, Gomer CJ, Triche TJ, Reynolds CP: Loss of p53 function confers high-level multi-drug resistance in neuroblastoma cell lines. Cancer Research 61:6185-6193, 2001.
  8. Anderson C, Reynolds CP: Syngergistic cytotoxicity of buthionine sulfoximine (BSO) and melphalan/BSO in combination for neuroblastoma cell lines derived after myeloablative therapy. Bone Marrow Transplantation 30:135-140, 2002.
  9. Villablanca JG, Krailo M, Ames MM, Bagniewski PG, Reid JM, Reynolds CP: A phase I trial of oral (capsular) fenretinide (NSC #374551) in children with high-risk solid tumors (Childrens Cancer Group Study 09709) J Clinical Oncology 24:3423-3430, 2006.
  10. Keshelava N, Davicioni E, Zesheng Wan Z, Ji L, Sposto R, Triche TJ, Reynolds CP: Inhibition of histone deacetylase (HDAC) 1, a drug target identified by expression profiling, sensitizes multi-drug-resistant neuroblastoma cell lines to cytotoxic agents. J National Cancer Institute 99:1107-19, 2007.
  11. Frgala T, Kalous O, Proffitt RT, Reynolds CP: A novel cytotoxicity assay with a 4 log dynamic range that identifies synergistic drug combinations. Molecluar Cancer Therapeutics 6:886-89, 2007.
  12. Maurer BJ, Kalous O, Yesair DW, Wu X, Vratilova J, Maldonado V, Khankaldyyan V, Frgala T, Sun BC, McKee RT, Burgess SW, Shaw WA, Reynolds CP: Improved oral delivery of N-(4-hydroxyphenyl)retinamide with novel LYM-X-SORB™ organized lipid complex in mice. Clinical Cancer Research 13:3079-3086, 2007.
  13. Kang MH, Kang YH, Szymanska B, Wilczynska-Kalak U, Sheard MA, Harned T, Lock RB, Reynolds CP: Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood 110:205-2066, 2007.
  14. Kang MH, Wan Z, Kang YH, Locke RS, Reynolds CP: Mechanism of synergy of N-(4-hydroxyphenyl)retinamide and ABT-737 in acute lymphoblastic leukemia cell lines: Mcl-1 inactivation. J National Cancer Institute 100:580-595, 2008.
  15. Cheung E, Dorff T, Groshen S, Quinn DI, Reynolds CP, Maurer BJ, Lara PN, Tsao-Wei DD, Twardowski P, Gandara DR, Chatta G, McNamara M, Pinski J: Oral fenretinide in biochemically recurrent prostate cancer: A California Cancer Consortium Phase II trial. Clinical Genitourinary Cancer 7:43-50, 2009.
  16. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger RC, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM: Anti-GD2 antibody with GM-CSF, IL2 and isotretinoin for neuroblastoma: A Children’s Oncology Group (COG) phase III study. New England J Medicine 363:1324-1333, 2010. (Faculty of 1000 ranked this paper in top 2% of biology and medicine published papers.)
  17. Kang MH, Smith MA, Morton CL, Nino Keshelava N, Houghton PJ, Reynolds CP: National Cancer Institute Pediatric Preclinical Testing Program: Model description for in vitro cytotoxicity testing. Pediatr Blood Cancer (EPUB Oct, 2010).
  18. Hadjidaniel MD and Reynolds CP: Antagonism of cytotoxic chemotherapy in neuroblastoma cell lines by retinoic acid is mediated by the anti-apoptotic Bcl-2 family proteins. Mol Cancer Therapeutics 9:3164-74, 2010.
  19. Kapranov P, St. Laurent G, Raz T, Fatih Ozsolak F, Reynolds CP, Sorensen PHB, Reaman G, Milos P, Arceci RJ, Thompson JF, Triche TJ: The majority of total nuclear-encoded non-ribosomal RNA in a human cell is “dark matter” unannotated RNA BMC Biology 8:149 [Epub] 2010
  20. Reynolds CP, Kang MH, Keir ST, Gorlick R, Kolb EA, Lock R, Maris JM, Carol H, Morton CL, Billups CA, MS, Smith MA, MD, Houghton PJ: Initial testing of lenalidomide by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer (In Press, 2010).

Current Grant Support

Grants as Principal Investigator

NCI RO1 (CA82830) Enhancing the Activity of Alkylating Agents in Neuroblastoma 1/05-12/11
NCI Contract Pediatric Preclinical Testing Program In Vitro Drug Testing Laboratory 11/04-10/14
NCCF Ewings Sarcoma Preclinical Testing Lab 01/11-12/12
USAMRMC 06213001 (DOD) Genome-wide Screening for Therapeutic Targets in Childhood Cancer: Preclinical Testing Core 9/07-10/13
NCI/NCCF COG Neuroblastoma cell culture laboratory 11/08-10/12
Cancer Prevention & Research Institute of Texas (CPRIT): RP10072 Enhancing the anti-neuroblastoma activity of fenretinide by identifying and targeting sphingolipid pathways that confer resistance. 9/10-8/13

Grants as Co-Investigator

CPRIT Kang, M (PI) MCL-1 Promoter Deletion in ALL 6/10-5/13
Wilson Foundation Maurer, BJ (PI) Preclinical Studies of fenretinide in ovarian cancer 11/10-10/11