A.        Positions and Honors

 

Positions and Employment

1973-1975       Intern and Resident in Medicine, Columbia-Presbyterian Hospital, New York, NY

1975-1977       Clinical Associate, Immunology Branch of the National Cancer Institute, Bethesda, MD

1977-1978       Clinical Fellow in Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

1979-1981       Instructor in Medicine, Harvard Medical School, Boston, MA

1981-1984       Assistant Professor of Medicine, Harvard Medical School, Boston, MA

1984-1992       Associate Professor of Medicine, Harvard Medical School, Boston, MA

1992-               Professor of Medicine, Harvard Medical School, Boston, MA

1993-1996       Chief, Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA

1996-1997       Chief, Experimental Oncology, Dana-Farber Cancer Institute, Boston, MA

1997-               Chief, Division of Medical Oncology, Brigham and Women's Hospital, Boston, MA

1997-2001       Chair, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA

2001-                             Senior Vice President, Experimental Medicine, Dana-Farber Cancer Institute, Boston, MA

2002-                   Virginia and D.K. Ludwig Professor of Medicine, Harvard Medical School

2003-                   Director, Center for Clinical and Translational Research, Dana-Farber Cancer Institute, Boston, MA

 

Honors

1989    The American Society for Clinical Investigation

1998    AACR Richard and Hinda Rosenthal Foundation Award

2000            Association of American of Physicians

2002      AACR Joseph H. Burchenal Clinical Research Award

2002        Virginia and D.K. Ludwig Professor of Medicine, Harvard Medical School

2002    Pan Mass Challenge Senior Investigator, Dana-Farber Cancer Institute

 

B.     Selected peer-reviewed publications (in chronological order).

1.      Freedman AS, Freeman G, Horowitz JC, Daley J and Nadler LM. B7, a B cell restricted antigen which identifies pre-activated B cells. J Immunol 1987; 137: 3260-3267.

2.      Nadler LM, Stashenko P, Hardy R, Kaplan WB, Button LN, Kufe DW, Antman KH and Schlossman SF. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res 1980; 40:3147-3154.

3.      Nadler LM, Stashenko P, Ritz J, Hardy R, Pesando JM and Schlossman SF. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest 1981; 67:134-140.

4.      Nadler LM, Stashenko P, Hardy R, van Agthoven A, Terhorst C and Schlossman SF. Characterization of a human B cell specific antigen (B2) distinct from B1. J Immunol 1981; 126: 1941-1947.

5.      Nadler LM, Anderson KC, Marti G, Bates M, Park E, Daley JF and Schlossman SF. B4, a human B cell associated antigen expressed on normal, mitogen activated, and malignant B lymphocytes. J Immunol 1983; 131: 244-250.

6.      Anderson KC, Slaughenhoupt B, Bates MP, Pinkus G, O'Hara C, Schlossman SF and Nadler LM. Expression of human B cell associated antigens on leukemia and lymphomas: A model of human B cell differentiation. Blood 1984; 63:1424-1433.

7.      Nadler LM, Korsmeyer SJ, Anderson KC, Boyd AW, Slaughenhoupt B, Park E, Jensen J, Coral F, Mayer RJ, Sallan SE, Ritz J and Schlossman SF. The B cell origin of non-T cell acute lymphoblastic leukemia: A model for discrete stages of neoplastic and normal pre-B cell differentiation. J Clin Invest 1984; 74: 332-340.

8.      Nadler LM, Takvorian T, Botnick L, Bast RC, Finberg R, Hellman S, Canellos GP and Schlossman SF. Anti-B1 monoclonal antibody and complement treated autologous bone marrow transplantation for relapsed B cell non-Hodgkin's lymphoma. Lancet 1984; 427-430.

9.      Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman S and Nadler LM. Prolonged disease-free survival in patients with poor prognosis non-Hodgkins lymphoma following autologous bone marrow transplantation. N Engl J Med l987; 3l6: 1499-1505.

10.  Freeman GF, Freedman AS, Segil J, Lee G, Whitman JF and Nadler LM. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol 1989; 143: 2714-2722.

11.  Freedman AS, Munro JM, Rice GE, Bevilacqua MP, Morimoto C, McIntyre BW, Rhynhart K, Pober JS and Nadler LM. Human B cell localization to germinal centers is mediated through VLA-4 and the adhesion molecule INCAM-110. Science 1990; 249: 1030-1033.

12.  Gimmi CD, Freeman GJ, Gribben JG, Sugita K, Freedman AS, Morimoto C and Nadler LM. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci, USA 1991; 88: 6575-6579.

13.  Gribben JG, Freedman AS, Neuberg D, Roy DC, Blake K, Woo SD, Grossbard ML, Coral F, Freeman GJ, Ritz J and Nadler LM. Immunologic purging of polymerase chain reaction detectable lymphoma cells results in increased disease-free survival following autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma. N Engl J Med 1991; 325: 1526-1533.

14.  Freeman GJ, Gribben JG, Boussiotis VA, Ng JW, Restivo Jr. VA, Lombard LA, Gray GS and Nadler LM. Cloning of B7-2, a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 1993; 262: 907-909.

15.  Boussiotis VA, Barber DL, Nakari T, Freeman GJ, Gribben JG, Bernstein GM, D'Andrea AD, Ritz J and Nadler LM. Prevention of T cell anergy by signaling through the cg chain of the IL-2 receptor. Science 1994; 266: 1039-1042.

16.  Gribben JG, Guinan EC, Boussiotis VA, Ke XY, Linsley L, Sieff, C, Gray GS, Freeman GJ and Nadler LM. Complete blockade of B7 family - Mediated costimulation is necessary to induce human alloantigen-specific anergy: A method to ameliorate graft-versus-host disease and extend the donor pool. Blood 1996; 87: 4887-4893.

17.  Boussiotis VA, Freeman GJ, Berezovskaya A, Barber DL and Nadler LM. Maintenance of human T cell anergy: Blocking of IL-2 gene transcription by activated Rap1. Science, 1997; 278: 124-128.

18.  Guinan EC, Boussiotis V, Neuberg D, LaVita Brennan L, Hirano N, Nadler LM and Gribben JG. Transplantation of anergic histoincompatible bone marrow allografts. N. Eng. J. Med., 1999; vol. 340: 1704-1714.

19.  Vonderheide RH, Hahn WC, Schultze JL and Nadler LM. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 1999; 10: 673-679.

20.  Boussiotis VA, Freeman GJ, Taylor PA, Berezovskaya A, Grass I, Blazar BR and Nadler LM. p27^kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes. Nature Medicine 2000, 6: 290-297.

21.  Maecker B, Sherr DH, Vonderheide RH, von Bergwelt-Baildon MS, Hirano N, Anderson KS, Xia Z, Butler M, Wucherpfennig KW, O'Hara C, Cole G, Kwak SS, Ramstedt U, Tomlinson AJ, Chicz RM, Nadler LM and Schultze JS.  The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells.   Blood 2003; 10:1182

22.  Vonderheide RH, Domchek SM, Schultze JL, George DJ, Hoar KM, Chen DY, Stephans KF, Masutomi K, Loda M, Xia Z, Anderson KS, Hahn WC and Nadler LM. Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res. 2004 Feb 1; 10(3): 828-839.

23.  Gribben JG, Ryan DP, Boyajian R, Urban RG, Hedley ML, Beach K, Nealon P, Matulonis U, Campos S, Gilligan TD, Richardson PG, Marshall B, Neuberg D and Nadler LM.  Induction of immunity to the universal tumor antigen CYP1B1 (ZYC300) primes for response to salvage therapy. Clin Cancer Res. 2005 Jun 15;11(12):4430-4436.

24.  Hirano N, Butler MO, Xia Z, von Bergwelt-Balidon MS, Freeman GJ and Nadler LM.  Engagement of CD83 ligand induces prolonged expansion of CD8+ T-cell and preferential enrichment for antigen specificity. (in revision)

25.  Butler MO, Nadler LM and Hirano N.  Ex vivo generation of long lived tumor associated-antigen specific CD8+ T cells. (submitted)

26.  Hirano N, Butler MO, Xia Z, Kohima S and Nadler LM.  Identification of g-globin derived peptide as a HLA-A2 restricted tumor-associated antigen for juvenile myelomonocytic leukemia. (in preparation).

27.  Hirano N, Butler MO and Nadler LM.  N-terminus but not C-terminus CBD is required for the extracellular expression and secretion of Galectin-8. (in preparation).

28.  Hirano N, Butler MO and Nadler LM.  Alpha 2-macroglobulin induces secretion of Galectin-8 via non-classical secretion pathway. (in preparation).

29.  Hirano N, Butler MO, Xia Z and Nadler LM.  Highly effective presentation ofnaturally processed class I peptides by artificial APC for the generation of effective anti-tumor responses.  (in preparation)

 

 

C.        Research Support.

 

Ongoing Research Support

Active  

 

Active  

 

Dana-Farber Cancer Institute   

Non-research related clinical, administrative, service and institutional support.

 

Cancer Center Support Grant*

Deputy Associate Director for Clinical Science                      ($15,594)         7.5%     

Deputy Associate Director, Planning & Evaluation                ($7,797)         3.75%

Considering the breadth of managing the existing and developing Disease-based Programs, Dr. Nadler will be directly responsible for leading the integration of Disease-based Programs with the Disciple-based Programs, with the view to fostering translational research.

*We have not yet received the notice of grant award for the new year, but we will very shortly*

 

NIH/NCI (Nadler, PI – PPG, Project 6, Core A)        Total grant:  $3,024,890

Rebuilding Immunity for Survival

Specific Control of Donor Anti-Host Alloreactivity

The specific aims of Project 6 are:                  ($173,649)       10%

1)     To undertake clinical trials to evaluate the capacity of adoptively transferred donor T cells anergized to host alloantigens to rapidly reconstitute a broad functional T cell repertoire.

2)     To improve control of donor anti-host alloreactivity ex vivo by manipulating additional pathways involved in the induction and maintenance of anergy.

3)     To determine which of the ex vivo approaches to control alloreactivity developed in Specific Aim 2 maximize retention of the pathogen specific repertoire and function.

Administrative Core

The purpose of Core A is to:                                      ($262,534)       10%

Support the Program Leaders and co-Leaders and their Programmatic administrative staff.

 

 

5MO1 RR02635* (Gottlieb, MD)             4/1/05 – 3/31/10                   10%

NIH/NCRR  (Nadler, Associate Program Director)                            ($23,193)

General Clincal Research Center                                     

 

The mission is to provide the infrastructure for patient-oriented research to be conducted at the Dana-Farber Cancer Institute and the Brigham and Women’s hospital.

*  Agreement with Dr. Nadler’s subcontract is in process of being finalized with BWH.

 

NIH/NCI (Nadler, PI – Project 6)                         ($251,701)

Currently operating under no-cost extension*       

Therapeutic Index of Acute Lymphoblastic Leukemia

The major goals of Project 6 are:

1.      To undertake clinical trials using vaccination and/or adoptive therapy to induce or augment       autologous T cell mediated anti-ALL specific immunity to determine feasibility, safety and clinical outcome.

2.      To develop pre-clinical strategies to modulate angiogenesis within the bone marrow of patients with ALL with the view to undertake clinical trials.

 

 

NIH  (Nadler, PI - Project 4)                 ($221,545)

Currently on no cost extension

Chronic Lymphocytic Leukemia Research Consortium     

The specific aims of Project 4 are:

1.      To attempt to determine the mechanism whereby T cells in patients with CLL are induced to become immune-incompetent.

2.      To examine the signaling events that follow CD40 ligation necessary and sufficient to induce competent antigen presentation by CLL cells.

3.      To develop and optimize methodologies to generate and expand autologous T cells and to undertake clinical trials of adoptive immunotherapy.

4.      To develop and optimize methodologies to generate and expand allogeneic T cells for adoptive immunotherapy following allogeneic stem cell transplantation (SCT).

5.      To determine the impact of autologous or allogeneic adoptive T cell immunotherapy in patients with minimal disease assessing PCR as a surrogate endpoint, relapse, and survival.