Sign in to edit your profile (add interests, mentoring, photo, etc.)
    Keywords
    Last Name
    Institution

    Michelle A Kelliher PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCancer Biology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-8620
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentMicrobiology and Physiological Systems

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCancer Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

        Overview 
        Narrative

        Apoptosis and cancer

        Mouse models of leukemia

        Michelle Kelliher PhD

        Aberrant expression of developmentally important regulatory genes has been increasingly implicated among hematopoietic malignancies. Abnormalities in either abundance or activity of these gene products can result in inappropriate expression of genes critical to the processes of cell growth and differentiation. I have been studying the basic domain helix-loop-helix (bHLH) family of transcription factors including TAL1, TAL2, LYL1 and E2A, all of which are associated with human leukemia. The overall goal of my research is to assess how these bHLH proteins contribute to disease development using the mouse as a model system.

        Most cases of pediatric T cell acute lymphoblastic leukemia (T-ALL) involve tumor specific activation of the bHLH gene TAL1/SCL. Ectopic expression of tal1 in the thymus of mice results in the development of clonal T cell leukemia/lymphoma. The TAL-1 protein, normally expressed in hematopoietic progenitors and erythroid cells, binds DNA once bound to E proteins (e.g. E47 and HEB), critical bHLH transcription factors which regulate lymphoid development. Stable tal1/E47 heterodimers are detected in mouse leukemic cells, suggesting that tal1 may contribute to leukemia by interfering with E protein function(s). Consistent with this idea, E2A-deficient mice and mice expressing a DNA binding mutant of tal-1 develop disease (O'Neil et al., 2001). A specific focus of our research is to ask whether tal1 transforms by interfering with E protein function(s) and to identify E47/HEB target genes de-regulated by tal1 expression. An additional objective is to identify genes that collaborate with tal1 to induce leukemogenesis, using retroviral insertional mutagenesis. We have identified retroviral insertions in notch 1, myc and ikaros loci and are currently testing whether expression of these genes accelerates tal1-induced leukemogenesis.

        The E2A locus is also the target of two chromosomal translocations associated with human leukemia. The t(17;19) translocation generates the chimeric fusion protein E2A-HLF which contains the transactivation domains of E2A and the bZIP domain of hepatic leukemia factor (HLF). To mimic the human translocation and to create a mouse model of E2A-HLF-induced leukemogenesis, wehave generated an E2A-HLF "knock-in" mouse. Mice homozygous for E2A-HLF exhibit defects in B cell development, consistent with studies of E2A-deficient mice. To determine if E2A-HLF expression predisposes mice to the development of leukemia weare performing chemical mutagenesis.

        The death domain kinase Rip1 in TNF and Toll receptor signaling

        Another area of research in my laboratory involves study of apoptosis or programmed cell death and how deregulation of this process contributes to the development of malignancy. We are studying a death domain kinase Rip1 which participates in TNF signaling. To define the contribution of Rip1 to TNF signaling, we adopted a genetic approach and created rip1-deficient mice. Murine embryonic fibroblasts that lack rip are highly sensitive to TNF-induced cell death due to an impaired NF-kB response (Kelliher et al., 1998). However, the introduction of a kinase defective allele of rip1 into rip-/- cells rescues the NF-kB defect, suggesting that the kinase activity of rip is not required for TNF-induced NF-kB activation. To elucidate the role of the kinase activity of rip1, we are identifying rip1 kinase substrates and have generated embryonic stem (ES)cells that express only kinase inactive Rip1.

        Recent work in the lab has also implicated Rip1 in Toll receptor 3 induced NF-kB activation. Rip1 deficient cells fail to activate NF-kB orinduce cytokine production when stimulated with double stranded RNA such as poly IC. Rip1 does not mediate IRF3 activation but activates NF-kB by associating with theTrif adapter protein. Current studies in the lab are focused on whether Rip1 also mediates MAPK activation or apoptosis in response to TLR3 activation.

        Figures

        Figure 1

        Models of transformation by the tal-1/scl oncogene. The inhibition model psotulates that ectopic expression of tal-1 in the thymus disrupts E47/HEB transcription of genes critical for thymocyte differentiation. The transactivation model suggests that novel oncogenes are induced by tal-1/E47 heterodimer. Both models may contribute to tal-1/scl leukemogenesis.

        Figure 2


        Rotation Projects

        Potential Rotation Projects

        Mechanism(s) of Leukemogenesis

        Project 1: We have used retroviral insertional mutagenesis to identify genes that collaborate with the basic helix-loop-helix b(HLH) tal-1/scl oncogene. Using genomic DNA from retrovirally-infected tumors, you will use inverse PCR to isolate and identify the collaborating oncogenes.

        Project 2: Using IPCR, we have identified the notch 1 locus as a frequent site for retroviral integration in Mo-MLV-infected tal-1/scl transgenic mice. To test whether expression of an activated notch1 allele accelerates tal-1/scl-induced leukemogenesis, you will reconstitute mice with wt or tal-1/scl hematopoietic precursors infected with a control or an activated notch1 retrovirus. The effects of notch and tal-1/scl expression on thymocyte development will be examined. If disease acceleration is observed, tumor cell lines will be established from mice to examine how notch1 and tal-1/scl proteins collaborate to induce disease in mice.

        TNF signaling in mouse development and cancer

        Project 1: Using Affymetrix oligonucleotide arrays, we have identified a number of novel, TNF-responsive genes. To determine the contribution of these genes to mouse development and TNF signaling, we have used gene targeting in embryonic stem cells to generate mice deficient for one of these genes. Sensitivity to TNF-induced cell death as well as IKK, jnk and p38 MAP kinase activation in response to TNF needs to be examined in murine embryonic fibroblasts derived from this mouse.

        Project 2: The death domain kinase RIP1 mediates the NF-kB repsonse to TNF, yet the kinase activity of RIP1 does not appear required. These studies suggest RIP1 may mediate IKK activation by recruiting another as yet unidentified kinase. Using biochemical approaches, you will isolate and identify proteins that interact with RIP1.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Kelliher for additional details.

        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Polykratis A, Hermance N, Zelic M, Roderick J, Kim C, Van TM, Lee TH, Chan FK, Pasparakis M, Kelliher MA. Cutting Edge: RIPK1 Kinase Inactive Mice Are Viable and Protected from TNF-Induced Necroptosis In Vivo. J Immunol. 2014 Aug 15; 193(4):1539-43.
          View in: PubMed
        2. Dillon CP, Weinlich R, Rodriguez DA, Cripps JG, Quarato G, Gurung P, Verbist KC, Brewer TL, Llambi F, Gong YN, Janke LJ, Kelliher MA, Kanneganti TD, Green DR. RIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3. Cell. 2014 May 22; 157(5):1189-202.
          View in: PubMed
        3. Weng D, Marty-Roix R, Ganesan S, Proulx MK, Vladimer GI, Kaiser WJ, Mocarski ES, Pouliot K, Chan FK, Kelliher MA, Harris PA, Bertin J, Gough PJ, Shayakhmetov DM, Goguen JD, Fitzgerald KA, Silverman N, Lien E. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. Proc Natl Acad Sci U S A. 2014 May 20; 111(20):7391-6.
          View in: PubMed
        4. Gutierrez A, Roderick JE, Kelliher MA. Leukemia propagating cells akt up. Cancer Cell. 2014 Mar 17; 25(3):263-5.
          View in: PubMed
        5. Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet. 2014 Apr; 46(4):364-70.
          View in: PubMed
        6. Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL, Harris MH, Silverman LB, Sallan SE, Gutierrez A, Look AT, Qi J, Bradner JE, Kelliher MA. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood. 2014 Feb 13; 123(7):1040-50.
          View in: PubMed
        7. Mavrogiorgos N, Mekasha S, Yang Y, Kelliher MA, Ingalls RR. Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response. Innate Immun. 2014; 20(4):377-89.
          View in: PubMed
        8. Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD, Brand M, Gutierrez A, Kelliher MA, Jamieson CH, von Boehmer H, Young RA, Look AT. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med. 2013 Jul 29; 210(8):1545-57.
          View in: PubMed
        9. Lukens JR, Vogel P, Johnson GR, Kelliher MA, Iwakura Y, Lamkanfi M, Kanneganti TD. RIP1-driven autoinflammation targets IL-1a independently of inflammasomes and RIP3. Nature. 2013 Jun 13; 498(7453):224-7.
          View in: PubMed
        10. Sanda T, Tyner JW, Gutierrez A, Ngo VN, Glover J, Chang BH, Yost A, Ma W, Fleischman AG, Zhou W, Yang Y, Kleppe M, Ahn Y, Tatarek J, Kelliher MA, Neuberg DS, Levine RL, Moriggl R, Müller M, Gray NS, Jamieson CH, Weng AP, Staudt LM, Druker BJ, Look AT. TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013 May; 3(5):564-77.
          View in: PubMed
        11. Sawai CM, Freund J, Oh P, Ndiaye-Lobry D, Bretz JC, Strikoudis A, Genesca L, Trimarchi T, Kelliher MA, Clark M, Soulier J, Chen-Kiang S, Aifantis I. Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia. Cancer Cell. 2012 Oct 16; 22(4):452-65.
          View in: PubMed
        12. Simmons MJ, Serra R, Hermance N, Kelliher MA. NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary tumorsphere-forming activity in vitro. Breast Cancer Res. 2012; 14(5):R126.
          View in: PubMed
        13. Sanda T, Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, Gutierrez A, Ma W, Tatarek J, Ahn Y, Kelliher MA, Jamieson CH, Staudt LM, Young RA, Look AT. Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia. Cancer Cell. 2012 Aug 14; 22(2):209-21.
          View in: PubMed
        14. Fortes GB, Alves LS, de Oliveira R, Dutra FF, Rodrigues D, Fernandez PL, Souto-Padron T, De Rosa MJ, Kelliher M, Golenbock D, Chan FK, Bozza MT. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood. 2012 Mar 8; 119(10):2368-75.
          View in: PubMed
        15. Tatarek J, Cullion K, Ashworth T, Gerstein R, Aster JC, Kelliher MA. Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL. Blood. 2011 Aug 11; 118(6):1579-90.
          View in: PubMed
        16. Yang Y, Xia F, Hermance N, Mabb A, Simonson S, Morrissey S, Gandhi P, Munson M, Miyamoto S, Kelliher MA. A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol Cell Biol. 2011 Jul; 31(14):2774-86.
          View in: PubMed
        17. Draheim KM, Hermance N, Yang Y, Arous E, Calvo J, Kelliher MA. A DNA-binding mutant of TAL1 cooperates with LMO2 to cause T cell leukemia in mice. Oncogene. 2011 Mar 10; 30(10):1252-60.
          View in: PubMed
        18. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med. 2010 Nov; 16(11):1321-7.
          View in: PubMed
        19. Ashworth TD, Pear WS, Chiang MY, Blacklow SC, Mastio J, Xu L, Kelliher M, Kastner P, Chan S, Aster JC. Deletion-based mechanisms of Notch1 activation in T-ALL: key roles for RAG recombinase and a conserved internal translational start site in Notch1. Blood. 2010 Dec 16; 116(25):5455-64.
          View in: PubMed
        20. Coulombe F, Divangahi M, Veyrier F, de Léséleuc L, Gleason JL, Yang Y, Kelliher MA, Pandey AK, Sassetti CM, Reed MB, Behr MA. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med. 2009 Aug 3; 206(8):1709-16.
          View in: PubMed
        21. Pandey AK, Yang Y, Jiang Z, Fortune SM, Coulombe F, Behr MA, Fitzgerald KA, Sassetti CM, Kelliher MA. NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog. 2009 Jul; 5(7):e1000500.
          View in: PubMed
        22. Cullion K, Draheim KM, Hermance N, Tammam J, Sharma VM, Ware C, Nikov G, Krishnamoorthy V, Majumder PK, Kelliher MA. Targeting the Notch1 and mTOR pathways in a mouse T-ALL model. Blood. 2009 Jun 11; 113(24):6172-81.
          View in: PubMed
        23. Ramnarain DB, Paulmurugan R, Park S, Mickey BE, Asaithamby A, Saha D, Kelliher MA, Mukhopadhyay P, Banani F, Madden CJ, Wright PS, Chakravarty S, Habib AA. RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR. Cell Death Differ. 2008 Feb; 15(2):344-53.
          View in: PubMed
        24. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher MA. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007 Dec 14; 282(50):36223-9.
          View in: PubMed
        25. Abbott DW, Yang Y, Hutti JE, Madhavarapu S, Kelliher MA, Cantley LC. Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains. Mol Cell Biol. 2007 Sep; 27(17):6012-25.
          View in: PubMed
        26. Sharma VM, Draheim KM, Kelliher MA. The Notch1/c-Myc pathway in T cell leukemia. Cell Cycle. 2007 Apr 15; 6(8):927-30.
          View in: PubMed
        27. Huye LE, Ning S, Kelliher M, Pagano JS. Interferon regulatory factor 7 is activated by a viral oncoprotein through RIP-dependent ubiquitination. Mol Cell Biol. 2007 Apr; 27(8):2910-8.
          View in: PubMed
        28. Sharma VM, Calvo JA, Draheim KM, Cunningham LA, Hermance N, Beverly L, Krishnamoorthy V, Bhasin M, Capobianco AJ, Kelliher MA. Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Mol Cell Biol. 2006 Nov; 26(21):8022-31.
          View in: PubMed
        29. Chang PY, Draheim K, Kelliher MA, Miyamoto S. NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells. Cancer Res. 2006 Jun 15; 66(12):6008-13.
          View in: PubMed
        30. Shank-Calvo JA, Draheim K, Bhasin M, Kelliher MA. p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice. Oncogene. 2006 May 18; 25(21):3023-31.
          View in: PubMed
        31. O'Neil J, Calvo J, McKenna K, Krishnamoorthy V, Aster JC, Bassing CH, Alt FW, Kelliher M, Look AT. Activating Notch1 mutations in mouse models of T-ALL. Blood. 2006 Jan 15; 107(2):781-5.
          View in: PubMed
        32. Cusson-Hermance N, Khurana S, Lee TH, Fitzgerald KA, Kelliher MA. Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem. 2005 Nov 4; 280(44):36560-6.
          View in: PubMed
        33. Das S, Cho J, Lambertz I, Kelliher MA, Eliopoulos AG, Du K, Tsichlis PN. Tpl2/cot signals activate ERK, JNK, and NF-kappaB in a cell-type and stimulus-specific manner. J Biol Chem. 2005 Jun 24; 280(25):23748-57.
          View in: PubMed
        34. Vivarelli MS, McDonald D, Miller M, Cusson N, Kelliher M, Geha RS. RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation. J Exp Med. 2004 Aug 2; 200(3):399-404.
          View in: PubMed
        35. O'Neil J, Shank J, Cusson N, Murre C, Kelliher M. TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB. Cancer Cell. 2004 Jun; 5(6):587-96.
          View in: PubMed
        36. Lee TH, Shank J, Cusson N, Kelliher MA. The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J Biol Chem. 2004 Aug 6; 279(32):33185-91.
          View in: PubMed
        37. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004 May; 5(5):503-7.
          View in: PubMed
        38. Lee TH, Huang Q, Oikemus S, Shank J, Ventura JJ, Cusson N, Vaillancourt RR, Su B, Davis RJ, Kelliher MA. The death domain kinase RIP1 is essential for tumor necrosis factor alpha signaling to p38 mitogen-activated protein kinase. Mol Cell Biol. 2003 Nov; 23(22):8377-85.
          View in: PubMed
        39. O'Neil J, Ventura JJ, Cusson N, Kelliher M. NF-kappaB activation in premalignant mouse tal-1/scl thymocytes and tumors. Blood. 2003 Oct 1; 102(7):2593-6.
          View in: PubMed
        40. Cusson N, Oikemus S, Kilpatrick ED, Cunningham L, Kelliher M. The death domain kinase RIP protects thymocytes from tumor necrosis factor receptor type 2-induced cell death. J Exp Med. 2002 Jul 1; 196(1):15-26.
          View in: PubMed
        41. O'Neil J, Billa M, Oikemus S, Kelliher M. The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice. Oncogene. 2001 Jun 28; 20(29):3897-905.
          View in: PubMed
        42. Lin Y, Devin A, Cook A, Keane MM, Kelliher M, Lipkowitz S, Liu ZG. The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of IkappaB kinase and c-Jun N-terminal kinase. Mol Cell Biol. 2000 Sep; 20(18):6638-45.
          View in: PubMed
        43. Devin A, Cook A, Lin Y, Rodriguez Y, Kelliher M, Liu Z. The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity. 2000 Apr; 12(4):419-29.
          View in: PubMed
        44. Smith D, Shang F, Nowell TR, Asmundsson G, Perrone G, Dallal G, Scott L, Kelliher M, Gindelsky B, Taylor A. Decreasing ascorbate intake does not affect the levels of glutathione, tocopherol or retinol in the ascorbate-requiring osteogenic disorder shionogi rats. J Nutr. 1999 Jun; 129(6):1229-32.
          View in: PubMed
        45. Scrofano MM, Shang F, Nowell TR, Gong X, Smith DE, Kelliher M, Dunning J, Mura CV, Taylor A. Calorie restriction, stress and the ubiquitin-dependent pathway in mouse livers. Mech Ageing Dev. 1998 Nov 16; 105(3):273-90.
          View in: PubMed
        46. Scrofano MM, Shang F, Nowell TR, Gong X, Smith DE, Kelliher M, Dunning J, Mura CV, Taylor A. Aging, calorie restriction and ubiquitin-dependent proteolysis in the livers of Emory mice. Mech Ageing Dev. 1998 Apr 1; 101(3):277-96.
          View in: PubMed
        47. Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity. 1998 Mar; 8(3):297-303.
          View in: PubMed
        48. Kelliher MA, Seldin DC, Leder P. Tal-1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha. EMBO J. 1996 Oct 1; 15(19):5160-6.
          View in: PubMed
        49. Kelliher MA, Weckstein DJ, Knott AG, Wortis HH, Rosenberg N. ABL oncogenes directly stimulate two distinct target cells in bone marrow from 5-fluorouracil-treated mice. Oncogene. 1993 May; 8(5):1249-56.
          View in: PubMed
        50. Kelliher M, Knott A, McLaughlin J, Witte ON, Rosenberg N. Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol. 1991 Sep; 11(9):4710-6.
          View in: PubMed
        51. Kelliher MA, McLaughlin J, Witte ON, Rosenberg N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A. 1990 Sep; 87(17):6649-53.
          View in: PubMed
        For assistance with using Profiles, please refer to the online tutorials or contact UMMS Help Desk or call 508-856-8643.
        Michelle's Networks
        Click the "See All" links for more information and interactive visualizations!
        Concepts
        _
        Co-Authors
        _
        Similar People
        _
        Same Department
        Physical Neighbors
        _

        This is an official Page/Publication of the University of Massachusetts Worcester Campus
        Office of the Vice Provost for Research, 55 Lake Ave North, Worcester, Massachusetts 01655
        Questions or Comments? Email: publicaffairs@umassmed.edu Phone: 508-856-1572