Education:
- Undergraduate: College of Charleston, BS, 1965
- Postgraduate: Medical College of South Carolina, MD, 1969
- Internship: Medical University Hospital (Charleston, SC), 1970
- Residency: Medical University Hospital (Charleston, SC), 1971
- Fellowship: National Institutes of Health, 1971-74
Interests:
- Teaching: Biology of Neoplasia, Morphologic Methods in Cell Biology
- Research: Molecular Mechanisms of Resistance to Cancer Therapy. Clinical: Molecular Markers of Cancer, Targeted Immunotoxins
Current Research:
Recent Publications:
Zhu X, Lee J-Y, Timmins JM, Brown JM, Boudyguina E, Mulya A, Gebre AK, Willingham MC, Hiltbold EM, Mishra N, Maeda N, Parks JS. Increased cellular free cholesterol in macrophage-specific Abca1 knockout mice enhances pro-inflammatory response of macrophages. J Biol Chem. 2008 Jun 14;[Epub ahead of print]
Mallakin A, Sugiyama T, Taneja P, Matise LA, Frazier DP, Choudhary M, Hawkins GA, D'Agostino RB Jr, Willingham MC, Inoue K. Mutually Exclusive Inactivation of DMP1 and ARF/p53 in Lung Cancer. Cancer Cell. 2007 Oct;12(4):381-94.
Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham MC, Pastan I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007 Sep 1;13(17):5144-9.
Van Emburgh BO, Hu JJ, Levine EA, Mosley LJ, Case LD, Lin HY, Knight SN, Perrier ND, Rubin P, Sherrill GB, Shaw CS, Carey LA, Sawyer LR, Allen GO, Milikowski C, Willingham MC, Miller MS. Polymorphisms in drug metabolism genes, smoking, and p53 mutations in breast cancer. Mol Carcinog. 2007 Aug 7; [Epub ahead of print]
Furuya F, Lu C, Willingham MC, Cheng SY. Inhibition of phosphatidylinositol 3' kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer. Carcinogenesis. 2007 Jul 28; [Epub ahead of print]
Ying H, Willingham MC, Cheng SY. The steroid receptor coactivator-3 is a tumor promoter in a mouse model of thyroid cancer. Oncogene. 2007 Jul 23; [Epub ahead of print]
Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest. 2007 Jul;117(7):1968-78.
Ho M, Bera TK, Willingham MC, Onda M, Hassan R, FitzGerald D, Pastan I. Mesothelin expression in human lung cancer. Clin Cancer Res. 2007 Mar 1;13(5):1571-5.
Das S, Hahn Y, Nagata S, Willingham MC, Bera TK, Lee B, Pastan I. NGEP, a prostate-specific plasma membrane protein that promotes the association of LNCaP cells. Cancer Res. 2007 Feb 15;67(4):1594-601.
Kim CS, Ying H, Willingham MC, Cheng SY. The pituitary tumor-transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer. Carcinogenesis. 2007 May;28(5):932-9.
Hicks AM, Willingham MC, Du W, Pang CS, Old LJ, Cui Z. Effector mechanisms of the anti-cancer immune responses of macrophages in SR/CR mice. Cancer Immun. 2006 Oct 31;6:11.
Ying H, Furuya F, Zhao L, Araki O, West BL, Hanover JA, Willingham MC, Cheng SY. Aberrant accumulation of PTTG1 induced by a mutated thyroid hormone beta receptor inhibits mitotic progression. J Clin Invest. 2006 Nov 1;116(11):2972-2984.
Stehle JR Jr, Weeks ME, Lin K, Willingham MC, Hicks AM, Timms JF, Cui Z. Mass spectrometry identification of circulating alpha-1-B glycoprotein, increased in aged female C57BL/6 mice. Biochim Biophys Acta. 2006 Jul 25; [Epub ahead of print]
Mallakin A, Taneja P, Matise LA, Willingham MC, Inoue K. Expression of Dmp1 in specific differentiated, nonproliferating cells and its regulation by E2Fs. Oncogene. 2006 Jul 31; [Epub ahead of print]
Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J, Simpson AJG, Old LG, Cui Z. Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. Proc Nat Acad Sci. 2006 May 16;103(20):7753-8.
Yu L, Bharadwaj S, Brown JM, Ma Y, Du W, Davis MA, Michaely P, Liu P, Willingham MC, Rudel LL. Cholesterol-regulated translocation of Niemann-pick C1-like 1 to the cell surface facilitates free cholesterol uptake.
J Biol Chem. 2006 Mar 10;281(10):6616-24.
Kato Y, Ying H, Zhao L, Furuya F, Araki O, Willingham MC, Cheng SY. PPARgamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappaB signaling pathway. Oncogene. 2006 May 4;25(19):2736-47.
Stehle JR Jr, Willingham MC, Lin K, Cui Z. A nonterminal method for frequent collection of mouse circulating proteins by peritoneal lavage. Anal Biochem. 2006 Feb 1;349(1):162-4. Epub 2005 Nov 9.
O'Flaherty JT, Rogers LC, Paumi CM, Hantgan RR, Thomas LR, Clay CE, High K, Chen YQ, Willingham MC, Smitherman PK, Kute TE, Rao A, Cramer SD, Morrow CS. 5-Oxo-ETE analogs and the proliferation of cancer cells. Biochim Biophys Acta. 2005 Oct 1;1736(3):228-36.
Ying H, Furuya F, Willingham MC, Xu J, O'Malley BW, Cheng SY. Dual functions of the steroid hormone receptor coactivator 3 in modulating resistance to thyroid hormone. Mol Cell Biol. 2005 Sep;25(17):7687-95.
Hassan R, Kreitman RJ, Pastan I, Willingham MC. Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol. 2005 Sep;13(3):243-7.
Shen YJ, Delong CJ, Terce F, Kute T, Willingham MC, Pettenati MJ, Cui Z. Polyploid Formation via Chromosome Duplication Induced by CTP:Phosphocholine Cytidylyltransferase Deficiency and Bcl-2 Overexpression: Identification of Two Novel Endogenous Factors. J Histochem Cytochem. 2005 Jun;53(6):725-33.
Bleyer AJ, Hart TC, Willingham MC, Iskandar SS, Gorry MC, Trachtman H. Clinico-pathologic findings in medullary cystic kidney disease type 2. Pediatr Nephrol. 2005 Jun;20(6):824-7.
Liu TF, Hall PD, Cohen KA, Willingham MC, Cai J, Thorburn A, Frankel AE. Interstitial diphtheria toxin-epidermal growth factor fusion protein therapy produces regressions of subcutaneous human glioblastoma multiforme tumors in athymic nude mice. Clin Cancer Res. 2005 Jan 1;11(1):329-34.
Westcott MM, Abi-Habib RJ, Cohen KA, Willingham MC, Liu S, Bugge TH, Leppla SH, Frankel AE. Diphtheria toxin-murine granulocyte-macrophage colony-stimulating factor-induced hepatotoxicity is mediated by Kupffer cells. Mol Cancer Ther. 2004 Dec;3(12):1681-9.
Furumoto H, Ying H, Chandramouli GV, Zhao L, Walker RL, Meltzer PS, Willingham MC, Cheng SY. An unliganded thyroid hormone beta receptor activates the cyclin D1/cyclin-dependent kinase/retinoblastoma/E2F pathway and induces pituitary tumorigenesis. Mol Cell Biol. 2005 Jan;25(1):124-35.
Parini P, Davis M, Lada AT, Erickson SK, Wright TL, Gustafsson U, Sahlin S, Einarsson C, Eriksson M, Angelin B, Tomoda H, Omura S, Willingham MC, Rudel LL. ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver. Circulation. 2004 Oct 5;110(14):2017-23.
Li J, Codina J, Petroske E, Werle MJ, Willingham MC, DuBose TD Jr. The effect of beta-subunit assembly on function and localization of the colonic H+,K+-ATPase alpha-subunit. Kidney Int. 2004 Sep;66(3):1068-75.
Kato Y, Ying H, Willingham MC, Cheng SY. A Tumor Suppressor Role for Thyroid Hormone {beta} Receptor in a Mouse Model of Thyroid Carcinogenesis. Endocrinology. 2004 Oct;145(10):4430-8.
Cui Z, Willingham MC. Halo Nevus: a visible immunosurveillance response against neoplasia in humans? Lancet Oncol. 2004 Jul;5(7):397-8.
Molnar I, Kute T, Willingham MC, Schwartz GG. 19-Nor-1alpha,25-dihydroxyvitamin D(2) (paricalcitol) exerts anticancer activity against HL-60 cells in vitro at clinically achievable concentrations. J Steroid Biochem Mol Biol. 2004 May;89-90:539-43.
Bhat S, Zabalawi M, Willingham MC, Shelness GS, Thomas MJ, Sorci-Thomas MG. Quality control in the apoA-I secretory pathway: deletion of apoA-I helix 6 leads to the formation of cytosolic phospholipid inclusions. J Lipid Res. 2004 Jul;45(7):1207-20.
Xu M, Floyd HS, Greth SM, Chang WC, Lohman K, Stoyanova R, Kucera GL, Kute TE, Willingham MC, Miller MS. Perillyl alcohol-mediated inhibition of lung cancer cell line proliferation: potential mechanisms for its chemotherapeutic effects. Toxicol Appl Pharmacol. 2004 Mar 1;195(2):232-46.
Trupiano JK, Geisinger KR, Willingham MC, Manders P, Zbieranski N, Case D, Levine EA.
Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers. Mod Pathol. 2004 Apr;17(4):476-81.
Schwartz GG, Eads D, Rao A, Cramer SD, Willingham MC, Chen TC, Jamieson DP, Wang L, Burnstein KL, Holick MF, Koumenis C. Pancreatic cancer cells express 25-Hydroxyvitamin D-1{alpha}-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3. Carcinogenesis. 2004 Jun;25(6):1015-26.
Cui Z, Willingham MC. The effect of aging on cellular immunity against cancer in SR/CR mice. Cancer Immunol Immunother. 2004 Jun;53(6):473-8.
Urieto JO, Liu T, Black JH, Cohen KA, Hall PD, Willingham MC, Pennell LK, Hogge DE, Kreitman RJ, Frankel AE. Expression and purification of the recombinant diphtheria fusion toxin DT388IL3 for phase I clinical trials. Protein Expr Purif. 2004 Jan; 33(1): 123-33.
Cartee L, Kucera GL, Willingham MC. Induction of apoptosis by gemcitabine in BG-1 human ovarian cancer cells compared with induction by staurosporine, paclitaxel and cisplatin. Apoptosis. 1998 Dec; 3(6): 439-49.
Liu TF, Cohen KA, Willingham MC, Tatter SB, Puri RK, Frankel AE. Combination fusion protein therapy of refractory brain tumors: demonstration of efficacy in cell culture. J Neurooncol. 2003 Oct; 65(1): 77-85.
Liu TF, Willingham MC, Tatter SB, Cohen KA, Lowe AC, Thorburn A, Frankel AE. Diphtheria toxin-epidermal growth factor fusion protein and Pseudomonas exotoxin-interleukin 13 fusion protein exert synergistic toxicity against human glioblastoma multiforme cells. Bioconjug Chem. 2003 Nov-Dec;14(6):1107-14.
Ying H, Suzuki H, Zhao L, Willingham MC, Meltzer P, Cheng SY. Mutant thyroid hormone receptor beta represses the expression and transcriptional activity of peroxisome proliferator-activated receptor gamma during thyroid carcinogenesis. Cancer Res. 2003 Sep 1; 63(17): 5274-80.
Raval GN, Bharadwaj S, Levine EA, Willingham MC, Geary RL, Kute T, Prasad GL. Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis, in primary breast tumors. Oncogene. 2003 Sep 18;22(40):6194-203.
Sweatt AJ, Wood M, Suryawan A, Wallin R, Willingham MC, Hutson SM. Branched-Chain Amino Acid Catabolism: Unique Segregation of Pathway Enzymes in Organ Systems and Peripheral Nerves. Am J Physiol Endocrinol Metab. 2003 Sep 9 [Epub ahead of print]
Wheeler YY, Kute TE, Willingham MC, Chen SY, Sane DC. Intrabody-based strategies for inhibition of vascular endothelial growth factor receptor-2: effects on apoptosis, cell growth, and angiogenesis. FASEB J. 2003 Sep;17(12):1733-5.
Liu TF, Tatter SB, Willingham MC, Yang M, Hu JJ, Frankel AE. Growth factor receptor expression varies among high-grade gliomas and normal brain: epidermal growth factor receptor has excellent properties for interstitial fusion protein therapy. Mol Cancer Ther. 2003 Aug;2(8):783-7.
Kamiya Y, Zhang XY, Ying H, Kato Y, Willingham MC, Xu J, O'Malley BW, Cheng SY. Modulation by steroid receptor coactivator-1 of target-tissue responsiveness in resistance to thyroid hormone. Endocrinology. 2003 Sep;144(9):4144-53.
Ying H, Suzuki H, Furumoto H, Walker R, Meltzer P, Willingham MC, Cheng SY. Alterations in genomic profiles during tumor progression in a mouse model of follicular thyroid carcinoma. Carcinogenesis. 2003 Sep;24(9):1467-79.
Cui Z, Willingham MC, Hicks AM, Alexander-Miller MA, Howard T, Hawkins G, Miller MS, Weir HM, Du W, DeLong CJ. Spontaneous regression of advanced cancer: Identification and characterization of a genetically-determined, age-dependent trait in mice. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6682-6687. A printable version of the article is available here; the free Adobe reader is required to download this file
Molnar I, Kute T, Willingham MC, Powell BL, Dodge WH, Schwartz GG. 19-Nor-1alpha,25-dihydroxyvitamin D(2) (paricalcitol): effects on clonal proliferation, differentiation, and apoptosis in human leukemic cell lines. J Cancer Res Clin Oncol. 2003 Jan;129(1):35-42.
Suzuki H, Zhang XY, Forrest D, Willingham MC, Cheng SY. Marked potentiation of the dominant negative action of a mutant thyroid hormone receptor {beta} in mice by the ablation of one wild-type {beta} allele. Mol Endocrinol. 2003 May;17(5):895-907.
Black JH, McCubrey JA, Willingham MC, Ramage J, Hogge DE, Frankel AE. Diphtheria toxin-interleukin-3 fusion protein (DT(388)IL3) prolongs disease-free survival of leukemic immunocompromised mice. Leukemia. 2003 Jan;17(1):155-9.
Suzuki H, Willingham MC, Cheng SY. Mice with a mutation in the thyroid hormone receptor Beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis. Thyroid. 2002 Nov;12(11):963-9.
Mahadev K, Raval G, Bharadwaj S, Willingham MC, Lange EM, Vonderhaar B, Salomon D, Prasad GL. Suppression of the transformed phenotype of breast cancer by tropomyosin-1. Exp Cell Res. 2002 Sep 10;279(1):40-51.
Wade WN, Willingham MC, Koumenis C, Cramer SD. p27Kip1 is essential for the antiproliferative action of 1,25-Dihydroxyvitamin D3 in primary, but not immortalized, mouse embryonic fibroblasts. J Biol Chem. 2002 Oct 4;277(40):37301-6.
Greene BT, Thorburn J, Willingham MC, Thorburn A, Planalp RP, Brechbiel MW, Jennings-Gee J, Wilkinson J 4th, Torti FM, Torti SV. Activation of caspase pathways during iron chelator-mediated apoptosis. J Biol Chem. 2002 Jul 12;277(28):25568-75.
Lada AT, Willingham MC, St Clair RW. Triglyceride depletion in THP-1 cells alters cholesteryl ester physical state and cholesterol efflux. J Lipid Res. 2002 Apr;43(4):618-28.
Torti SV, Golden-Fleet M, Willingham MC, Ma R, Cline M, Sakimoto Y, Torti FM. Use of green fluorescent protein to measure tumor growth in an implanted bladder tumor model. J Urol. 2002 Feb;167(2 Pt 1):724-8.