Graduate Program Information
My Contact Information

Professor of Biochemistry and Biophysics
Ph.D. Rutgers University 1955

Hormone action is mediated by specific cell receptors, resulting in a variety of metabolic responses and/or growth. A number of hormones are implicated in the etiology and growth of mammary cancer. Our studies are directed towards elucidation of the roles of estrogens and antiestrogens, insulin and insulin-like growth factors (IGFS) as regulators of neoplastic growth. By utilizing well characterized rodent models, in vivo and in vitro, experiments are designed to gain understanding of these regulatory actions.

Mechanism of action of estrogens and antiestrogens is being studied by defining the nucleotide requirements for binding of estrogen and antiestrogen activated estrogen receptor with their DNA regulatory element (ERE) and by transfection assays. Estrogen response depends on the expression level of one or both estrogen receptor (ER) isoforms, alpha and beta, and the concentration and type of ER-ligands. Our goal is to understand how these factors contribute to the level of induction characteristic of a particular gene. We have now established that insulin affects tumor growth and regulation, both directly and in a permissive role. We have examined insulin and estrogen receptors, how they are regulated by hormones and how such regulation relates to changes in tumor growth behavior.

A second active area of study is to define the mechanisms whereby tumor cytotoxicity ensues photoradiation therapy, a treatment approach that employs hematoporphyrin photosensitizers followed by exposure of tumors to visible light. The singlet oxygen produced is cytotoxic. We reported that important cellular targets are several mitochondrial respiratory enzymes, leading to reduced ATP production. Current aims are to elucidate these actions and to evolve methods to optimize therapeutic efficacy. The role of estrogenic and antiestrogenic agents in altering production of protoporphyrin IX from 5-aminolevulinic acid and the actions of new synthetic prophyrin derivatives are ongoing projects aimed at improving PDT outcome.

Recent Publications

Hilf R (2007) Mitochondria are targets of photodynamic therapy. J Bioenerg Biomembr, 39:85-9

Huang J, Li X, Qiao T, Bambara RA, Hilf R, Muyan M (2006) A tale of two estrogen receptors (ERs): how differential ER-estrogen responsive element interactions contribute to subtype-specific transcriptional responses. Nucl Recept Signal, 4:e015

Huang J, Li X, Maguire CA, Hilf R, Bambara RA, Muyan M (2005) Binding of estrogen receptor beta to estrogen response element in situ is independent of estradiol and impaired by its amino terminus. Mol Endocrinol, 19:2696-712

You Y, Gibson SL, Hilf R, Ohulchanskyy TY, Detty MR (2005) Core-modified porphyrins. Part 4: Steric effects on photophysical and biological properties in vitro. Bioorg Med Chem, 13:2235-51

Huang J, Li X, Hilf R, Bambara RA, Muyan M (2005) Molecular basis of therapeutic strategies for breast cancer. Curr Drug Targets Immune Endocr Metabol Disord, 5:379-96

Gibson SL, Hilf R, Donnelly DJ, Detty MR (2004) Analogues of tetramethylrosamine as transport molecules for and inhibitors of P-glycoprotein-mediated multidrug resistance. Bioorg Med Chem, 12:4625-31

Li X, Huang J, Yi P, Bambara RA, Hilf R, Muyan M (2004) Single-chain estrogen receptors (ERs) reveal that the ERalpha/beta heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways. Mol Cell Biol, 24:7681-94

Detty MR, Gibson SL, Hilf R (2004) Comparison of the dark and light-induced toxicity of thio and seleno analogues of the thiopyrylium dye AA1. Bioorg Med Chem, 12:2589-96

Detty MR, Prasad PN, Donnelly DJ, Ohulchanskyy T, Gibson SL, Hilf R (2004) Synthesis, properties, and photodynamic properties in vitro of heavy-chalcogen analogues of tetramethylrosamine. Bioorg Med Chem, 12:2537-44

Huang J, Li X, Yi P, Hilf R, Bambara RA, Muyan M (2004) Targeting estrogen responsive elements (EREs): design of potent transactivators for ERE-containing genes. Mol Cell Endocrinol, 218:65-78

You Y, Gibson SL, Hilf R, Davies SR, Oseroff AR, Roy I, Ohulchanskyy TY, Bergey EJ, Detty MR (2003) Water soluble, core-modified porphyrins. 3. Synthesis, photophysical properties, and in vitro studies of photosensitization, uptake, and localization with carboxylic acid-substituted derivatives. J Med Chem, 46:3734-47

Brennan NK, Hall JP, Davies SR, Gollnick SO, Oseroff AR, Gibson SL, Hilf R, Detty MR (2002) In vitro photodynamic properties of chalcogenopyrylium analogues of the thiopyrylium antitumor agent AA1. J Med Chem, 45:5123-35

Sathya G, Yi P, Bhagat S, Bambara RA, Hilf R, Muyan M (2002) Structural regions of ERalpha critical for synergistic transcriptional responses contain co-factor interacting surfaces. Mol Cell Endocrinol, 192:171-85

Hilmey DG, Abe M, Nelen MI, Stilts CE, Baker GA, Baker SN, Bright FV, Davies SR, Gollnick SO, Oseroff AR, Gibson SL, Hilf R, Detty MR (2002) Water-soluble, core-modified porphyrins as novel, longer-wavelength-absorbing sensitizers for photodynamic therapy. II. Effects of core heteroatoms and meso-substituents on biological activity. J Med Chem, 45:449-61

Yi P, Bhagat S, Hilf R, Bambara RA, Muyan M (2002) Differences in the abilities of estrogen receptors to integrate activation functions are critical for subtype-specific transcriptional responses. Mol Endocrinol, 16:1810-27

Yi P, Driscoll MD, Huang J, Bhagat S, Hilf R, Bambara RA, Muyan M (2002) The effects of estrogen-responsive element- and ligand-induced structural changes on the recruitment of cofactors and transcriptional responses by ER alpha and ER beta. Mol Endocrinol, 16:674-93

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry
Ph.D. in Biophysics
Ph.D. in Genetics
Ph.D. in Microbiology and Immunology

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: russell_hilf@urmc.rochester.edu

Russell Hilf
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 3-8555
Telephone: (585) 275-3085; Fax: (585) 275-6007