Nita J. Maihle, Ph.D.

Professor Departments of OB/Gyn and Reproductive Sciences, Pathology, and Pharmacology Phone: 203-787-1385 Fax: 203-737-2914 Email: nita.maihle@yale.edu Ti Badri, Research Assistant Phone: 203-737-1649 Email: ti.badri@yale.edu

Research Interests

Dr. Nita Maihle is an experienced cancer biologist who has devoted her career to developing a better understanding of what causes cancer, and to applying this information to improved methods for the care and treatment of cancer patients.  Over the past two decades, Dr. Maihle and her colleagues have discovered that the signals that cause cancer cells to grow are different from the signals that cause normal cells to grow.  These “short circuits” in cancer cells can be targeted to specifically stop cancer cells from growing.  New drugs targeting these cancer cell short circuits, drugs such as Herceptin and Gleevec, are some of the most cutting-edge, effective, and specific agents used in the treatment of cancer patients today.  Studies in Dr. Maihle’s laboratory are focused on making this list of new drugs grow even longer. 

In addition, these short circuits give cancer cells a molecular signature or profile that is unique to the cancer cell.  Dr. Maihle’s laboratory has developed exquisitely sensitive biochemical assays that may one day be useful in detecting cancer cells anywhere in the body using a simple blood test to detect the tumor long before it is clinically detectable.  Such early detection would allow even currently available treatments to be more effective—potentially alleviating much human suffering.  These early detection studies in Dr. Maihle’s laboratory are particularly advanced in breast and ovarian cancer patients, but also show great promise for prostate, pancreatic, and lung cancer, as well as in certain brain tumor patients. The National Cancer Institute has continuously funded Dr. Maihle’s important studies in this field for the past two decades.  Dr. Maihle is strongly committed to the clinical translation of basic research discoveries and is working with the private sector to bring these advances into the clinic.

Dr. Maihle has served as a mentor and role model for many successful students, residents, fellows, and visiting professors through the years, and has been particularly active as an advocate for women and other underrepresented individuals in the biomedical sciences.  She serves in a leadership capacity for numerous interdisciplinary cancer research organizations throughout the country, and also for several national research funding organizations.  She currently serves as Chair of the U.S. Dept. of Defense’s Ovarian Cancer Research Program, and also is a member of the Board of Scientific Counselors for the National Cancer Institute.

Selected Peer Reviewed Publications

Albitar, L., Pickett, G., Morgan, M., Wilken, J., Maihle, N., Leslie, K. (2008) EGFR Isoforms and Gene Regulation in Human Endometrial Cancer Cells. (In Process)

Lafky, J. M., Baron, A. and Maihle, N. J. (2008) Clinical Implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands. Biochim. Biophy. Acta (Cancer Reviews), (In press)

Dogan, S., Hu, X., Maihle, N.J., Grande, J.P., and Cleary, M.P. (2007) Effects of a high fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGFα mice.  Breast Cancer Research; 9:R91.

Fisher, M.C., Maihle, N.J., Clinton, G.M., and C.N. Dealy (2007) Requirement for ErbB2/ErbB signaling in developing cartilage and bone. Dev Growth Diff., 49: 503-513

Dickerson, D. Liu, A. Rademaker, D.A. Fishman, K.C. Podratz, J. McAlpine, and N.J. Maihle (2007) p110 soluble epidermal growth factor receptor (sEGFR): a biomarker of epithelial ovarian cancer. In Requisites in Obstetrics and Gynecology: Gynecologic Oncology, pp. 000-000, (In Press).

Cleary, M.P., Hu, X., Grossman, M.E., Juneja, S.C., Dogan, S.,Grande, J.P., and Maihle, N.J. (2007) Prevention of mammary tumorigenesis by intermittent caloric restriction: Does caloric intake during refeeding modulate the response? Exp Biol Med. 232(1):70-80.

Jones, M.B., Houwink, A.P., Freeman, B.K., Greenwood, T., Lafky, J.M., Lingle, W.L., Berchuck, A.,  Maxwell, G.L., Podratz, K.C., and Maihle, N.J. (2006) The granulin-epithelin precusor is a steroid-regulated growth factor in endometrial cancer. J Soc Gynecol Investig. 13(4):304-11.

Baron, A.T., and Maihle, N.J. (2005) Does the nadir CA 125 concentrations predict along-term outcome after chemotherapy for carcinoma of the ovary? Nature Clin. Pract. Onc. (6) 288-289.

*Lafky, J. M., *Baron, A. T., Cora, E. M., Hillman, D. W, Suman, V. J., Perez, E. A., Ingle, J. N., and Maihle, N. J. (2005) Serum sEGFR concentrations decrease in postmenopausal metastatic breast carcinoma patients treated with letrozole. Cancer Research 65: 3059-3062.

Omi, M., Fisher, M., Maihle, N. J., and Dealy, C. N. (2005) Studies on EGF receptor signaling in vertebrate limb patterning. Developmental Dynamics 233(2): 288-300.

Baron, A. T., Boardman, C. H., Lafky, J. M., Rademaker, A., Liu, D., Fishman, D. A.,Podratz, K. C., Maihle, N. J. (2005) Soluble epidermal growth factor receptor (sEGFR) and cancer antigen 125 (CA-125) as screening and diagnostic tests for epithelial ovarian cancer. Cancer Epidemiol. Biomarkers Prev, 14(2): 306-18.

Cleary, M.P., Grande, J.P., Juneja, S.C., and Maihle, N.J. (2004) Diet-induced obesity and mammary tumor development in MMTV-neu mice. Nutrition & Cancer, 50(2): 174-180.

Cleary, M. P., Grande, J. P., and Maihle, N. J. (2004) Effect of high fat diet on bodyweight and mammary tumor latency in MMTV-TGF-α mice. Intl. J. Obesity. 28: 956-962.

Cleary, M. P., Juneja, S.C., Phillips, F. C., Hu, X., Grande, J. P., and Maihle, N. J. (2004) Leptin receptor deficient MMTV-TGF-α-/LeprdbLeprdb female mice do not develop oncogene-induced mammary tumors. Exp. Biol. Med. 229(2):182-93.

Danielsen, A. J., Christensen, T. A., Lovejoy, C. A., Adelsman, M. A., Connolly, D. C.,and Maihle, N. J. (2003) Membrane localization is required for ligand-independent v-ErbB-mediated transformation. Exp. Cell. Res. 296(2):285-293.

Baron, A. T., Cora, E. M., Lafky, J. M., Boardman, C. H., Buenafe, M. C., Rademaker, A. W., Liu, D., Suman, V. J., Fishman, D. A., Podratz, K. C., and Maihle, N. J. 2003. Serum EGF receptor (sEGFR/sErbB1) as a potential risk, screening, and diagnostic biomarker of epithelial ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 12:1-11.

Boerner, J., Danielsen, A., and Maihle, N. J. 2003. Ligand-independent oncogenic signaling by the EGF receptor: vErbB as a paradigm. Exp. Cell Res. 284:111-121.

Boerner, J. L., *Danielsen, A. J., Lovejoy, C., A., Wang, Z., Juneja, S. C., Faupel-Badger, J. M., Darce, J.R., and Maihle, N. J. 2003. Grb2 regulation of the actin-based cytoskeleton is required for ligand independent EGF receptor-mediated oncogenesis. Oncogene 22:6679-6689.

Hu, X., Juneja, S., Maihle, N. J. and Cleary, M. P. 2002. Leptin stimulates breast cancer cell proliferation and Lep-1- mice are resistant to mammary tumorigenesis. J. Natl. Cancer Inst. 94:1704-1711.

Cleary, M. P., Jacobson, M. K., Phillips, F. C., Getzin, S. C., Grande, J. P., and Maihle, N. J. 2002. Weight-cycling decreases incidence and increases latency of mammary tumors to a greater extent than does chronic caloric restriction in MMTV-TGF-α female mice. Cancer Epidemiol. Biomarkers Prev. 11:836-843.

Baron, A. T., Lafky, J. M., Suman, V. J., Hillman, D. W., Buenafe, M. C., Boardman, C. H., Podratz, K. C., Perez, E. A., and Maihle, N. J. 2001. A preliminary study of serum concentrations of soluble epidermal growth factor receptor (sErbB1), gonadotropin, and steroid hormones in healthy men and women. Cancer Epidemiol. Biomarkers Prev. 10:1175-1185.

Lee, H., Akita, R.W., Sliwkowski, M.X. and Maihle, N.J. 2001. A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulin-stimulated activation of ErbB2, ErbB3, and ErbB4. Cancer Res. 61:4467-4473.

Boerner, J. L., Danielsen, A. J., McManus, M. J., and Maihle, N. J. 2001. Activation of RhoA is required for ligand-independent oncogenic signalling by a mutant EGF receptor. J. Biol. Chem. 276:3691-3695.

Reiter, J.L., Threadgill, D.W., Eley, G.D., Strunk K., Danielsen, A.J., Sinclair, C.S., Pearsall, R.S., Green, P.J., Yee, D., Lampland, A.L., Balasubramaniam, S., Crossley, T.O., Magnuson, T.R., James, C.D., and Maihle, N.J. 2001. Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms. Genomics 71:1-20.

McManus, M. J., Boerner, J.L., Danielsen, A.J., Wang, Z., Matsumura, F., and Maihle, N. J. 2000. An oncogenic EGF receptor signals via a p21-activated kinase-caldesmon-myosin phosphotyrosine complex. J. Biol. Chem. 275:35328-35334.