EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)

RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding with present position, list, in chronological order, previous employment, experience, and honors. Include present membership on any Federal Government public advisory committee. List, in chronological order, the titles, all authors, and
complete references to all publications during the past three years and to representative earlier publications pertinent to this application. If the list of
publications in the last three years exceeds two pages, select the most pertinent publications. DO NOT EXCEED TWO PAGES.

Professional Experience:

Brown University, Phi Beta Kappa and Magna Cum Laude                                                                        1961

Yale University School of Medicine, Alpha Omega Alpha & Cum Laude                                                    1965

Intern and Resident in Medicine, Harvard Medical Unit & Thorndike Labs,

      Boston City Hospital, Boston, MA (Max Finland, Chas Davidson, William Castle)                              1965-67

Clinical Assoc., Arthritis & Rheumatology Sec., NIAID, NIH (Edw. J. Leonard,, John Decker)                   1967-69

British American Heart Fellow, London Hosp. Med. Sch, London England (G. L. Asherson)                       1969-70

Postdoctoral Trainee, Inflammatory Disease, Yale Univ. (Fred S. Kantor)                                                   1970-71

U.S.P.H.S. Special Postdoctoral Fellow                                                                                                   1971-73

Assistant Professor of Medicine, Yale University School of Medicine                                                        1971-75

Allergic Diseases Academic Award (RDCA, NIAID)                                                                                1974-79

Associate Professor of Medicine, Yale University School of Medicine                                                        1975-82

Visiting Scientist, Immunoparasitology, Mill Hill London, UK (Bridget Oglivie)                                        1977-78

NIH Immunological Sciences Study Section, Member                                                                               1983-87

Professor of Medicine & Pathology, Yale University School of Medicine                                                    1983-pres.

Visiting Scientist, Tumor Immunol. Unit, Univ College, London, England (Mark Feldman)                         1984-85

Chief, Section of Allergy & Clinical Immunology, Yale University Dept. of Med.                                       1985-pres.

NIH MERIT Awardee, NIAID, Allergic Immunologic Diseases Program                                                    1987-1997.

Visiting Scientist, Molecular Immunology, Biology Dept, Yale U. (Adrian Hayday)                                    1990-1991

NIH, Allergy, Immunology & Transplantation Research Committee                                                           1992-96

Visiting Prof, Imperial College Med Sch, London (T. Williams, AB Kay, Fan Chung, D. Haskard)  1998-1999

Honors and Awards

Magna Cum Laude and Junior Phi Beta Kappa, Brown University, 1961

Cum Laude and Alpha Omega Alpha, Yale University School of Medicine 1965

British American Heart Fellow of the American Heart Association, 1969-1970

USPHS  Postdoctoral Traineeship 1970-1971

USPHS Special Postdoctoral Fellowship 1971-1973

NIAID Allergic Diseases Academic Award (Career Development Award) 1974-1979

Direct Election to Fellow, American Academy of Allergy, 1976

Recipient, Laurens Hammond Grant for Cancer Research 1975-1977

NIAID Merit Award, , Immunology, Allergic and Immunologic Diseases Program, 1987-1997

Foreign Corresponding Member of the Polish Academy of Arts & Sciences, 1992-present

Research Projects Ongoing or Completed During the Last 3 Years:

Title: “T cells in the Pathogenesis of Human Isocyanate (TDI) Asthma” Agency: NHLBI

PI for Subproject No. 6 is Carrie Redlich, MD,  Overall PI:  Jack Elias, MD

Type: SCOR NIH, P50-HL-56389; Period 12-1-96 to 11-30-01.

The goal of this subproject is to determine the pathogenesis of TDI-associated asthma in patients with development of in vitro assays to analyze the antigenic  determinants, T cell subsets, and cytokines that are involved in this occupational asthma.

Title: “Cytokines and endothelial adhesion molecules in hapten-induced airway hyper-responsiveness”,

PI for Subproject No. 5 is P. W. Askenase, MD, Overall PI: Jack Elias, MD, Agency: NHLBI

Type: SCOR NIH, P50-HL-56389; Period 12-1-96 to 11-30-01.

The goal of this Subproject is to determine the role of endothelial cell vascular activation and adhesion molecule expression in the airways of the lung, in the pathogenesis of a mouse model of asthma that we have developed.  Dr. Jordan Pober, an expert on lymphocyte-endothelial interactions, is an active co-investigator.

Title: “Role of B-1 B cells in acquired T cell Immunity”. PI: Philip W. Askenase, MD; Type: R01 #AI-43371, Duration 8/01/99 to 7/31/01, $160,000.  The goal of this project is to identify the role of IgM producing B-1 cells in the initiation of contact sensitivity.

Bibliography: (from a total of 157 original articles)

1.        Rankin JA, Hitchcock M, Merrill WW, and Askenase PW. Slow reacting substance: IgE-dependent release from alveolar macrophages. Nature 297:329, 1982.

2.        Brown SJ, Galli SJ, Gleich GJ, and Askenase PW. Abalation of immunity to Amblyoma Americanum by anti-basophil serum: co-operation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs. J. Immunol. 129:790, 1982.

3.        Mitchell EB, and Askenase PW. Suppression of T-cell mediated cutaneous basophil hypersensitivity by serum from guinea pigs immunized with mycobacterial adjuvant. J. Exp. Med. 156:159, 1982.

4.        Askenase PW, Rosenstein RW, and Ptak W. T cells produce an antigen-binding factor with in vivo activity analogous to IgE antibody. J. Exp. Med. 157:1604, 1983.

5.        Van Loveren H, Meade R, & Askenase PW. An early component of delayed-type hypersensitivity mediated by T cells and mast cells. J. Exp. Med. 157:1604, 1983.

6.        Van Loveren H, Kraeuter-Kops S, and Askenase PW. Different mechanisms of release of vasoactive amines by mast cells in T cell compared to IgE-dependent cutaneous hypersensitivity responses. Eur J Immunol. 14:40, 1984.

7.        Van Loveren H, and Askenase PW. Delayed-type hypersensitivity is mediated by a sequence of two different T cell activities. J. Immunol. 133:2397, 1984.

8.        Van Loveren H, Kato K, Meade R, Green DR, Horowitz M, Ptak W, and Askenase PW. Characterization of two different Ly-1⁺ T cell populations that mediate delayed-type hypersensitivity. J. Immunol. 133:2420, 1984.

9.        Brown SJ, and Askenase PW. Rejection of ticks from guinea pigs by anti-hapten antibody mediated degranulation of basophils at cutaneous basophil hypersensitivity sites: role of mediators other than histamine. J. Immunol. 134:1160, 1985.

10.     Van Loveren H, Den Otter W, Meade R, Terheggen PMS, and Askenase PW. A role for mast cells and the vasoactive amine serotonin in T cell-dependent immunity to tumors. J. Immun. 134:1292, 1985.

11.     Theoharides TC, Kraeuter-Kops S, Bondy PK, and Askenase PW.  Differential release of serotonin without comparable histamine can occur under diverse conditions in rat mast cells. Biochem. Pharmacol. 34:1398, 1985.

12.     Meade R, Van Loveren H, Parmentier H, Iverson GM, and Askenase PW. The antigen-binding T cell factor PCl-F sensitizes mast cells for in vitro release of serotonin: Comparison with monoclonal IgE antibody. J. Immunol. 141:2704-2713, 1988.

13.     Ameisen JC, Meade R, Askenase PW. A new interpretation of the involvement of serotonin in delayed-type hypersensitivity: Serotonin-2 receptor antagonists inhibit contact sensitivity by an effect on T cells. J. Immunol. 142:3171-3179, 1989.

14.     Herzog W, Meade R, Pettinicchi A, Ptak W, and Askenase PW. Nude mice produce a T cell-derived antigen-binding factor mediating early component of delayed-type hypersensitivity. J. Immunol. 142:1803-1812, 1989.

15.     Herzog WR, Ferreri NR, Ptak W, and Askenase PW.  The DTH-initiating Thy-1⁺ cell is double negative (CD4^-, CD8^-) and CD3^-, and expresses IL-3 receptors, but no IL-2 receptors. J. Immun.143:3125- 1989.

16.     Garssen J, Nijkamp FP, Wagenaar SS, Zwart A, Askenase PW, and Van Loveren H. Regulation of delayed-type hypersensitivity-like responses in the mouse lung, determined with histological procedures: serotonin, T-cell suppressor-induced factor and high antigen dose tolerance regulate the magnitude of T-cell dependent inflammatory reactions. Immunol, 68:51, 1989.

17.     Herzog WR, Millet I, Ferreri NR, Ramabhadran R, Schreurs J, and Askenase PW. An antigen-specific DTH-initiating cell clone. Functional, phenotypical, and partial molecular characterization. J. Immunol. 144:1, 1990.

18.     Ptak W, Herzog WR, and Askenase, PW.  Delayed-type hypersentivity initiation by early-acting cells antigen mismatched or MHC incompatable with late-acting, DTH effector T cells. J. Immunol. 146:469-475, 1991.

19.     Ptak W, Geba GP, and Askenase PW. Initiation of delayed-type hypersensitivity by low doses of monoclonal IgE antibody. J. Immunol. 146:3929-3936, 1991.

20.     Ptak W & Askenase PW. gd T cells assist ab T cells in transfer of contact sensitivity. J. Immunol. 149:3503-3508, 1992.

21.     Ferreri NR, Sarr T, Askenase PW, and Ruddle NH. Molecular regulation of tumor necrosis factor-a & lymphotoxin production in T cells: Inhibition by prostaglandin E₂.  J Bio Chem, 267:9443, 1992.

22.     Ferreri, NR, Herzog WR, and Askenase PW. Inhibition of IL-2-dependent proliferation by a prostaglandin-dependent suppressor factor. J. Immunol. 150:2102, 1993.

24.    Ishii N, Takahashi K, Nakajima H, Tanaka S, and Askenase PW.  DNFB contact sensitivity (CS) in BALB/c and C3H/He mice: requirement for early-occurring, early-acting, antigen-specific, CS-initiating cells with an unusual phenotype (Thy-1⁺, CD5⁺, CD3^-, CD4^-, CD8^-, sIg^-, B220⁺, MHC Class-II^-, CD23⁺, IL-2R^-, IL-3R⁺, Mel-14^-, Pgp-1⁺, J11d⁺, MAC-1⁺, LFA-1⁺, and FcgIIR⁺). Invest Derm 102:321-327, 1994.

25.     Paliwal V, Friedman AM, Ptak W, and Askenase PW. Monoclonal, antigen-specific, T cell contrasuppressor factor expresses determinants of T cell receptor (TCR) a chain (and not necessarily TCR b chain), and has a molecular size of about 40 kDa. Jo. Immunol. 152:2811-2820, 1994.

26.   Askenase PW, Szczepanik M, Ptak M, Paliwal V, and Ptak W. gd T cells in normal spleen assist immunized ab T cells in the adoptive cell transfer of contact sensitivity: effect of Bordetella pertussis, cyclophosphamide, and antisuppressor cells antibodies. J. Immunol. 154:3644, 1995.

27.    Murray AG, Petzelbauer P, Hughes CCW, Costa J, Askenase PW, and Pober JS. Human T cell mediated destruction of allogeneic dermal microvessels in a SCID mouse. Proc Nat Acad Sci USA, 91:9146-9150, 1995.

28.     Sperl J, Paliwal V, Ramabhadran R, Nowak B, and Askenase PW. Soluble T cell receptors: Detection and quantitative assay in fluid phase via ELISA or immuno-PCR. J. Immunol. Methods 186:181-194, 1995.

29.     Ptak W, Szczepanik M, Ramabhadran R, and Askenase PW. gd T cells assist ab T cells in transfer of contact sensitivity, preferentially employ Vg5 and Vd4 variable region gene segments. J. Immunol. 156:976-986, 1995.

30.     Szczepanik, M. Anderson LR, Ushio H, Ptak W, Owen MJ, Hayday AC, Askenase PW. gd T cells from tolerized ab T cell receptor (TCR)-deficient mice inhibit contact sensitivity-effector T cells in vivo, and their interferon-g production in vitro. J Exp Med. 184:2129-2139, 1996.

31.   Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, and Ra C. Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int. Immunol. 9:461-466, 1997.

32.   Paliwal V, Ptak W, Sperl J, Braswell E, and Askenase PW. Recombinant soluble ab T cell receptors protect T cells from immune suppression.  Requirement for aggregated multimeric, disulfide-linked ab heterodimers. J Immunol. 159:1718-1727, 1997.

33.   Tsuji RF, Geba GP, Wang, Y, Kawamoto K, Matis L, and Askenase PW. Required early  complement activation in contact sensitivity with generation of C5-dependent chemotactic activity and late T cell IFN-g: A possible initiating role of B cells.  J Exp Med. 186:1015-1026, 1997. 

34.   Sultan P, Schechner JS, McNiff JM, Hockman PS, Hughes CCW, Lorber MI, Askenase PW and Pober JS. Blockade of CD2-LFA-3 interactions protects human skin allografts in immunodeficient mouse/human chimeras. Nature BioTech. 15:759-762, 1997.

35.  Ushio H, Matsuda H, and Askenase PW.  IL-12 reverses established antigen-specific tolerance of contact sensitivity by affecting co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) J. Immunol. 160:2080-2088, 1997.

36.   Paliwal V, Ptak W, Sperl J, Braswell E, and Askenase PW. Recombinant soluble ab T cell receptors protect T cells from suppression: require aggregated multimeric, disulfide-linked ab heterodimers. J Imunol. 159:1718-1727, 1997.

37.   Geba GP, Wegner CD, Wolyniec W, Yining L, and Askenase PW. In vivo airway hyperreactivity adoptively transferred to naive mice by THY-1⁺ and B220⁺ antigen-specific cells that lack surface expression of CD3. J Clin Invest. 100:629-638, 1997.

38.   Tsuji RF, Geba GP, Wang Y, Kawamoto K, Matis L, and Askenase PW. Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell IFN-g: A possible initiating role of B cells., J. Exp. Med. 186:1015-1026, 1997.

39.     Murray AG, Schechner J, Epperson DE, Sultan P, McNiff JM, Hughes CWC, Lorber MI, Askenase PW and Pober JS.  Dermal microvascular injury in the Hu-PBL mouse/skin allograft model is T cell-mediated and inhibited by combination of cyclosporine and rapamycin. Amer Jo Pathol, 153:627, 1998.

40.     Lorber MI, Wilson JH, Robert ME, Schechner JS, Kirkiles N, Qian H-Y, Askenase PW, Tellides G, and Pober JS.  Human allogeneic vascular rejection after arterial transplantation and peripheral lymphoid reconstitution in SCID mice. Transplantation 67:897-903, 1999.

41.     Pober JS, Schechner JS, Murray AG, Sultan P, Kirkiles N, Tereb D, Wilson J, McNiff JM, Askenase PW, Tellides G, and Lorber MI.  Allogeneic and xenogeneic vascular injury and protection. Transplantation Proc. 30:4168-4169, 1998.

42.     Ying S, Robinson DS, Meng Q, Barata LT, McEuen AR, Buckley MG, Walls AF, Askenase PW, and Kay AB.  C-C chemokines in allergen-induced late phase cutaneous responses in atopic subjects: Association of eotaxin with early 6 hr eosinophils, and eotaxin-2 and MCP-4 with the later 24 hr tissue eosinophilia, and relationship to basophils and other C-C chemokines (MCP-3 and RANTES), Accepted for publication, J Immunol, 163:3976-3984, 1999.

43.     Szczepanik M, Ptak W, and Askenase PW.  Role of IL-4 in down-regulation of contact sensitivity by gd T cells from tolerized TCRa^-/- mice.  Immunology 98:63-70, 1999.

44.     Kawamoto K, Paliwal V, Ramabhadran R, Szczepanik M, Tsuji RF, Matsuda H, and Askenase PW.  IL-12 induced in APC by soluble ab TCR protects Th1 cells from suppression. International Immunol, 12:103-112, 2000.

45.     Harari OA, McHale JF, Marshall D, Ahmed S, Brown D, Askenase PW, and Haskard DO.  Endothelial cell E-and P-selectin up-regulation in murine contact sensitivity is prolonged by distinct mechanisms occurring in sequence. J. Immunol. 163:6860-6866, 1999.

46.     Tsuji RF, Kawikova I, Ramabhadran R, Akahira-Azuma M, Taub D, Hugli TE, Gerard C, Askenase PW. Early local generation of C5a initiates elicitation of contact sensitivity by leading to early T cell recruitment. J Immunol. 165:1588, 2000.

47.     Thomas MJ, MacAry PA, Noble A, Roy S, Askenase PW, and Kemeny DM. CD8 Tc1 and Tc2 T cells prevent IgE allergy via a novel IL-12 immune regulatory pathway. Submitted.

48.     Huang T-J, MacAry PA, Askenase PW, Kemeny DM, and Chung KF. Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation, partly via IFN-g. Submitted.