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    Mary M Lee MD

    TitleChair and Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentPediatrics
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-334-0526
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentCell and Developmental Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMasters in Clinical Investigation

        Overview 
        Narrative

        Biography

        M.D.,SUNY-Buffalo School of Medicine 1983
        Resident in Pediatrics, Children's Hospital of Buffalo 1983-1986
        Fellow, Pediatric Endocrinology and Metabolism, Children's Hospital of Philadelphia1986-1989
        Research fellow,Massachusetts General Hospital 1989-1992
        Assistant Professor of Pediatrics,Harvard Medical School, Boston, MA 1993-2000
        Associate Professor of Pediatrics, Duke University Medical Center, Durham, NC 2000-2004

        Prof of Pediatrics and Cell Biology
        Director, Ped Endo and Diabetes, UMass Medical School Current

        Mary Lee, MD

        Testicular Development

        We are interested in understanding the role of Mullerian inhibiting substance in the testis and elucidating the hormonal and cellular interactions that are critical for testicular development. Our research involves both clinical investigations and laboratory studies. Our basic research efforts have focused on clarifying the paracrine and endocrine regulation of Leydig cell differentiation and on identifying the effects of persistent organic pollutants (endocrine disruptors, such as dioxins) on the developing male reproductive system.

        Areas of research interest:

        • Biology and regulation of Mullerian inhibiting substance
        • Sexual differentiation and intersex disorders
        • Testicular differentiation and development (fetal and postnatal) of Leydig cells
        • The effects of environmental toxins on reproductive development
        • Gonadal toxicity of chemotherapy and radiation for childhood malignancies

        schematic MIS actions in Leydig cells

        Figure 1. Mullerian Inhibiting Substance (MIS) is a negative regulator of progenitor Leydig cell proliferation and differentation and an inhibitor of adult Leydig cell androgen biosynthesis.

        TUNEL staining testicular sections

        Figure 2. TUNEL staining of representative light micrographs of 4-µm-thick testicular sections from MIS and control-treated rats on Day 15 after EDS treatment. A) Control rat. B and C) MIS-treated rats. Most of the TUNEL-positive nuclei are located within the seminferous tubules and correspond to germ cells. Arrow: interstitial cell with TUNEL-positive nucleus. Scale bar = (A and B) 100µm and (C) 25µm. (Salva A, et al. Biology of Reproduction 2004;70:600-607)



        Rotation Projects

        Potential Rotations for Students

        1. Characterize the Leydig cell phenotype of different KO and transgenic models of specific genes relevant to reproductive development to determine the role of these genes in Leydig cell development: i.e. GPR54, androgen receptor, etc.
        2. Examine the mechanisms underlying the inhibitory effects of dioxin on Leydig cell steroidogenesis and investigate the developmental basis of this.
        3. Investigate the role of MIS in the development of Leydig cell tumors.
        4. Examine MIS signaling in Leydig cells.


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Zawatski W, Lee MM. Male pubertal development: are endocrine-disrupting compounds shifting the norms? J Endocrinol. 2013; 218(2):R1-R12.
          View in: PubMed
        2. Mitchell K, Johnson K, Cullen K, Lee MM, Hardy OT. Parental mastery of continuous subcutaneous insulin infusion skills and glycemic control in youth with type 1 diabetes. Diabetes Technol Ther. 2013 Jul; 15(7):591-5.
          View in: PubMed
        3. Wu X, Zhang N, Lee MM. Mullerian Inhibiting Substance Recruits ALK3 to Regulate Leydig Cell Differentiation. Endocrinology. 2012 Oct; 153(10):4929-37.
          View in: PubMed
        4. Sullivan-Bolyai S, Crawford S, Johnson K, Huston B, Lee MM. Educating diabetes camp counselors with a human patient simulator: a pilot study. J Spec Pediatr Nurs. 2012 Apr; 17(2):121-8.
          View in: PubMed
        5. Nwosu BU, Stavre ZG, Maranda L, Cullen K, Lee MM. Hepatic dysfunction is associated with vitamin D deficiency and poor glycemic control in diabetes mellitus. J Pediatr Endocrinol Metab. 2012; 25(1-2):181-6.
          View in: PubMed
        6. Nwosu BU, Meltzer B, Maranda L, Ciccarelli C, Reynolds D, Curtis L, King J, Frazier JA, Lee MM. A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics. J Pediatr Endocrinol Metab. 2011; 24(9-10):619-26.
          View in: PubMed
        7. Sullivan-Bolyai S, Lee MM. Parent mentor perspectives on providing social support to empower parents. Diabetes Educ. 2011 Jan-Feb; 37(1):35-43.
          View in: PubMed
        8. Nwosu BU, Soyka LA, Angelescu A, Lee MM. Evidence of insulin-like growth factor binding protein-3 proteolysis during growth hormone stimulation testing. J Pediatr Endocrinol Metab. 2011; 24(3-4):163-7.
          View in: PubMed
        9. Wu X, Arumugam R, Zhang N, Lee MM. Androgen profiles during pubertal Leydig cell development in mice. Reproduction. 2010 Jul; 140(1):113-21.
          View in: PubMed
        10. Nwosu BU, Lee MM. Pseudohypoparathyroidism type 1a and insulin resistance in a child. Nat Rev Endocrinol. 2009 Jun; 5(6):345-50.
          View in: PubMed
        11. Jacobson-Dickman E, Lee MM. The influence of endocrine disruptors on pubertal timing. Curr Opin Endocrinol Diabetes Obes. 2009 Feb; 16(1):25-30.
          View in: PubMed
        12. Nwosu BU, Lee MM. Evaluation of short and tall stature in children. Am Fam Physician. 2008 Sep 1; 78(5):597-604.
          View in: PubMed
        13. Wu X, Wan S, Pujar S, Haskins ME, Schlafer DH, Lee MM, Meyers-Wallen VN. A single base pair mutation encoding a premature stop codon in the MIS type II receptor is responsible for canine persistent Müllerian duct syndrome. J Androl. 2009 Jan-Feb; 30(1):46-56.
          View in: PubMed
        14. Wu X, Wan S, Lee MM. Key factors in the regulation of fetal and postnatal Leydig cell development. J Cell Physiol. 2007 Nov; 213(2):429-33.
          View in: PubMed
        15. Buchold GM, Magyar PL, Arumugam R, Lee MM, O'Brien DA. p19Ink4d and p18Ink4c cyclin-dependent kinase inhibitors in the male reproductive axis. Mol Reprod Dev. 2007 Aug; 74(8):997-1007.
          View in: PubMed
        16. Lee MM. Clinical practice. Idiopathic short stature. N Engl J Med. 2006 Jun 15; 354(24):2576-82.
          View in: PubMed
        17. Wu X, Arumugam R, Baker SP, Lee MM. Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice. Endocrinology. 2005 Feb; 146(2):589-95.
          View in: PubMed
        18. Hardy O, Worley G, Lee MM, Chaing S, Mackey J, Crissman B, Kishnani PS. Hypothyroidism in Down syndrome: screening guidelines and testing methodology. Am J Med Genet A. 2004 Feb 1; 124A(4):436-7.
          View in: PubMed
        19. Lee MM, Misra M, Donahoe PK, MacLaughlin DT. MIS/AMH in the assessment of cryptorchidism and intersex conditions. Mol Cell Endocrinol. 2003 Dec 15; 211(1-2):91-8.
          View in: PubMed
        20. Salva A, Hardy MP, Wu XF, Sottas CM, MacLaughlin DT, Donahoe PK, Lee MM. Müllerian-inhibiting substance inhibits rat Leydig cell regeneration after ethylene dimethanesulphonate ablation. Biol Reprod. 2004 Mar; 70(3):600-7.
          View in: PubMed
        21. Lee MM. Is treatment with a luteinizing hormone-releasing hormone agonist justified in short adolescents? N Engl J Med. 2003 Mar 6; 348(10):942-5.
          View in: PubMed
        22. Misra M, MacLaughlin DT, Donahoe PK, Lee MM. The role of Müllerian inhibiting substance in the evaluation of phenotypic female patients with mild degrees of virilization. J Clin Endocrinol Metab. 2003 Feb; 88(2):787-92.
          View in: PubMed
        23. Lee MM, Sergeyev O, Williams P, Korrick S, Zeilert V, Revich B, Hauser R. Physical growth and sexual maturation of boys in Chapaevsk, Russia. J Pediatr Endocrinol Metab. 2003 Feb; 16(2):169-78.
          View in: PubMed
        24. Litton J, Rice A, Friedman N, Oden J, Lee MM, Freemark M. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus. J Pediatr. 2002 Oct; 141(4):490-5.
          View in: PubMed
        25. Misra M, MacLaughlin DT, Donahoe PK, Lee MM. Measurement of Mullerian inhibiting substance facilitates management of boys with microphallus and cryptorchidism. J Clin Endocrinol Metab. 2002 Aug; 87(8):3598-602.
          View in: PubMed
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