Nicholas Heintz, Ph.D.

Professor of Pathology

Professor of Microbiology & Molecular Genetics

Research Programs: Cell Signaling & Growth Control
Genome Stability & Expression
VCC Membership Level: Member Scientist

Contact Information

Department of Pathology
University of Vermont
Burlington, VT 05405

ph: (802) 656-0372
f: (802) 656-8892
Nicholas.Heintz@uvm.edu

Biography

Dr. Heintz received his Ph.D. in 1979 from the University of Vermont, where he studied the effects of aflatoxin and other carcinogens on neoplastic transformation of hepatocytes. He then pursued postdoctoral training in molecular genetics with Joyce Hamlin at the University of Virginia. During this period, Dr. Heintz identified and cloned for the first time an origin of replication from mammalian cells. Since his return to UVM in 1983, Dr. Heintz has continued to focus on control of cell proliferation, with an emphasis on cell signaling events that control transition through G1 and entry into the S phase. Dr. Heintz has been an American Cancer Society Research Faculty Fellow, a Lake Champlain Cancer Research Organization J. Walter Juckett Fellow, and a visiting professor at the National Cancer Research Institute in Tokyo, Japan and the European Institute of Oncology in Milan, Italy.

Research

Dr. Heintz's laboratory studies the regulation of cell proliferation, with an emphasis on the pathways that control transition through G1 and entry into the S phase. They have recently focused on redox-dependent cell signaling pathways that are commonly deregulated in human cancers, with an emphasis on how endogenous and exogenous sources of reactive oxygen species influence the expression of cyclin D1, a critical regulator of cell proliferation. Recently the lab has examined the role of two important redox-dependent protein families in cancer cell biology: 1) NAPDH oxidases that contribute to the production of oxidants required for cell proliferation and migration in response to growth factors, and 2) peroxiredoxins, a family of antioxidant enzymes that are commonly deregulated in a wide variety of cancers, in cell signaling pathways that promote cell proliferation. Because human tumors often produce high levels of reactive oxygen species, the laboratory also is interested in how perturbations in redox signaling and cycling can be exploited to interfere with cell proliferation and migration in human tumors. The laboratory has also initiated a new project to study the effect of gene dosage on cell growth in carcinogenesis.

Research Supported by the Mesothelioma Applied Research Foundation.

Recent Publications

Janssen-Heininger YM, Mossman BT, Heintz NH, Forman HJ, Kalyanaraman B, Finkel T, Stamler JS, Rhee SG, van der Vliet A. Redox-based regulation of signal transduction: Principles, pitfalls, and promises. Free Radic Biol Med. 45:1-17, 2008.

Pantano C, Anathy V, Ranjan P, Heintz NH, Janssen-Heininger YM. Non-phagocytic oxidase 1 causes death in lung epithelial cells via a TNF-R1-JNK signaling axis. Am. J. Respir. Cell. Mol. Biol., 36:473-479, 2007.

Muss HB, Bunn JY, Crocker A, Plaut K, Koh J, Heintz N, Rincon M, Weaver D, Tam D, Beatty B, Kaufman P, Donovan M, Verbel D, Weiss L. Cyclin D-1, interleukin-6, HER-2/neu, transforming growth factor receptor-II and prediction of relapse in women with early stage, hormone receptor-positive breast cancer treated with tamoxifen. Breast J. 13:337-45, 2007.

Phalen TJ, Weirather K, Deming PB, Anathy V, Howe AK, van der Vliet A, Jonsson T, Poole LB, Heintz NH. Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery. J. Cell Biol. 175: 779-789, 2006.

Reynaert NL, van der Vliet A, Guala AS, McGovern T, Hristova M, Pantano C, Heintz NH, Heim J, Ho YS, Matthews DE, Wouters EF, Janssen-Heininger YM. Dynamic redox control of NF-kB through glutaredoxin-regulated S-glutathionylation of inhibitory kB kinase beta. Proc. Natl. Acad. Sci. 103:13086-13091, 2006.

Ranjan P, Anathy V, Burch PM, Weirather K, David Lambeth J, Heintz NH. Redox-dependent activation of cyclin D1 expression and mouse lung epithelial cell proliferation by Nox1. Antioxidants and Redox Signaling 8:1447-1459, 2006.

Ranjan P, Heintz NH. S phase arrest by reactive nitrogen species is bypassed by okadaic acid, an inhibitor of protein phosphatases PP1/PP2A. Free Radical Biology Medicine 40:24-259, 2006.

Sabo-Attwood T, Ramos-Nino M, Bond J, Butnor KJ, Heintz N, Gruber AD, Steele C, Taatjes DJ, Vacek P, Mossman BT. Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis. Amer. J. Pathology, 167:1243-1256, 2005.

Ramos-Nino ME, Vianale G, Sabo-Attwood T, Mutti L, Porta C, Heintz N, Mossman BT. Human mesothelioma cells exhibit tumor cell-specific differences in PI3-K/AKT activity that predict the efficacy of Onconase. Mol. Can. Ther. 4:835-842, 2005.

Rice TS, Ding M, Pederson DS, Heintz NH. The highly conserved tRNAHis guanylyltransferase Thg1p interacts with ORC and is required for the G2/M phase transition in yeast. Eukaryotic Cell 4:832-835, 2005.

Rice TS, Ding M, Pederson DS, Heintz NH. The highly conserved tRNAHis guanylyltransferase Thg1p interacts with ORC and is required for the G2/M phase transition in yeast. Eukaryotic Cell 4:832-835, 2005.

Yuan Z, Mossman BT, Taatjes D, Heintz NH. The duration of nuclear ERK1/2 signaling during cell cycle re-entry distinguishes proliferation from apoptosis in response to asbestos. Cancer Res. 64:6530-6536, 2004

Burch PM, Yuan Z, Loonen A, Heintz NH. An ERK1,2-dependent program of chromatin trafficking of c-Fos and Fra-1 is required for cyclin D1expression during cell cycle re-entry. Mol. Cell. Biol. 24:46-96-4709, 2004.

Park K-K, Ahn JD, Lee I-K, Magae J, Heintz NH, Kwak J-Y, Lee Y-C, Cho Y-S, Kim H-C, Chae Y-M, Kim YH, Kim C-H, Chang Y-C. Inhibitory effects of novel E2F decoy oligodeoxynucleotides on mesangial cell proliferation by coexpression of E2F/DP. Biochem. Biophys. Res. Comm. 308:689-697, 2003.

Yuan Z, Schellekens H, Warner L, Janssen-Heininger Y, Burch P, Heintz NH. Reactive nitrogen species block cell cycle reentry through sustained production of intracellular hydrogen peroxide. Am. J. Respir. Cell Mol. Biol. 28:705-712, 2003.