Download Wu_Catherine CV April 3 2013

CURRICULUM VITAE
Date Prepared:
June 2, 2013
Name:
Catherine Ju-Ying Wu
Office Address: Dana-Farber Cancer Institute
Harvard Institutes of Medicine
77 Avenue Louis Pasteur -- Room 420
Boston, MA 02115
Home Address: 117 Mason Terrace, Brookline MA 02446
Work Phone:
617 632-5943
Work Email:
[email protected]
Work FAX:
617-632-3351
Place of Birth:
New York City, NY
Education
1988
A.B.
Biochemistry
1994
M.D.
Medicine
Harvard University,
Cambridge, MA
Stanford University,
Stanford, CA
Postdoctoral Training
06/94-06/97
Resident
Medicine
Brigham &Women’s Hospital, Boston, MA
07/94-06/00
Clinical Fellow
Medicine
Harvard Medical School, Boston, MA
07/97-06/00
Fellow
Dana-Farber/Partners CancerCare, Boston MA
07/97-06/00
Clinical Fellow
Hematology/
Oncology
Medicine
Brigham &Women’s Hospital
Faculty Academic Appointments
07/00-02/06
Instructor
Medicine
Harvard Medical School
03/06-01/13
Assistant Professor
Medicine
Harvard Medical School
02/13present
Associate Professor
Medicine
Harvard Medical School
Appointments at Hospitals/Affiliated Institutions
07/00-
Active Staff
Medical Oncology
07/00-
Associate Physician
Medicine
Dana-Farber Cancer
Institute
Brigham and Women’s
Hospital
Committee Service
Local
1996-1999
Premedical Advisory Committee, Mather
House
1996-1998
1998-1999
Harvard College, Cambridge MA
2001
Internal Medicine Residency Program
Admissions Committee
Brigham and Women’s Hospital,
Member
2007-present
Harvard Premedical Society
Harvard College
Mentor
2008
PhD Thesis Committee (Tanya
Knickerbocker)
Harvard College, Chemistry Department,
Member
2013
PhD Thesis Committee (Sylvan Baca)
Division of Medical Sciences, Department
of Biological and Biomedical Sciences,
Harvard University
Chair and Resident Tutor
Non-resident Premedical Tutor
National
2008
NIH Consensus Conference on Sickle Cell
Disease, Sub-committee on Research
Priorities in Allotransplantation
NIH-National Heart, Lung and Blood
Institute, Bethesda MD
Member
2008-
External Eligibility Review Panel
Blood and Marrow Clinical Trials Network
Protocol 0601 (Unrelated donor
hematopoietic cell transplantation for
children with severe sickle cell disease
using a reduced intensity conditioning
regimen)
Member
2008-
Steering Committee
STRIDE (Sickle cell Transplantation to
2
Prevent Disease Exacerbation in Young
Adults) collaborative trial
Member
Professional Societies
2000American Society of Hematology
2008, 2009
2008
Member
Member, Abstract Selection Committee
Session Moderator
2000-
American Society of Blood and Marrow
Transplantation
2011
Member
2011-
American Association for Cancer Research
Member
2012-
American Society for Clinical Investigation
Member
2012-
Program in Leder Human Biology and
Translational Medicine, PhD Program in
Biological and Biomedical Science,
Harvard Medical School
Faculty member
Grant Review Activities
2008-2010
Medical Student Research Fellows Program
Member, Organizing and Abstract Selection
Committee
Howard Hughes Medical Institute, Bethesda
MD
Member
2009present
KL2 Medical Research Investigator
Training Award
Harvard Catalyst Program, Harvard Medical
School
Member
2011
Transplantation, Tolerance and Tumor
Immunity Study Section
NIH
Ad hoc Member
2012
Blood Cell Therapies Special Emphasis
Panel
NIH
Ad hoc Reviewer
2012
Scholar Award Study Section
American Society of Hematology
Ad hoc Reviewer
Editorial Activities
• Ad hoc Reviewer
3
Clinical Cancer Research
British Journal of Hematology
The Hematology Journal
Blood
Journal of Immunology
European Journal of Immunology
Molecular and Cellular Proteomics
New England Journal of Medicine
Leukemia
Honors and Prizes
1988
1988-89
1990
1998
1999
2000
Magna cum Laude
Graduate Scholarship
Stanford Medical
Scholars Research
Fellowship
Medical Student
Research Fellowship
Continuing Studies
Fellowship
Katherine McCormick
Research Award
Graduating Honors
Award
Graduating Honors
Award
Travel Award
Travel Award
Forbeck Scholar Award
2002
Travel Award
2010
Travel Award
1990-1991
1991-1993
1992
1994
1994
Harvard College
Rotary International, Nice, France
Stanford Medical School
Biochemistry
Biochemistry
Research
Howard Hughes Medical Institute
Research
Howard Hughes Medical Institute
Research
Stanford Medical School
Research
Stanford Medical School
Research
Stanford Medical School
Clinical Medicine
American Society of Hematology
American Society of Hematology
William G. Forbeck Research
Foundation
American Society of Blood and
Marrow Transplantation
American Society of Blood and
Marrow Transplantation
Research
Research
Research
Research
Research
Report of Funded and Unfunded Projects
Funding Information
Past
1999-2000
Serologic identification of antigens associated with the graft-versus-leukemia effect of
donor lymphocyte infusion (DLI) for relapsed chronic myelogenous leukemia (CML) after
bone marrow transplantation (BMT)
Howard Hughes Medical Institute, Postdoctoral Research Fellowship for Physicians.
4
PI ($130,000)
The major goal of this study is to characterize the humoral immune response developing
against antigens expressed on chronic myelogenous leukemia cells in association with
effective clinical responses to donor lymphocyte infusion (DLI).
2000-2005
Leukemia antigens following donor lymphocyte infusion
NIH- NHLBI/K08 HL04293-01 (Mentored Clinical Scientist Development Award)
PI ($589,625)
The major goals of this study are to characterize the gene expression patterns and the
antibody and T cell responses elicited by donor lymphocyte infusion-associated antigens.
2002-2007
Non-myeloablative stem cell transplant for severe hemoglobinopathies
Doris Duke Clinical Mentored Scientist Award
PI ($507,826)
The major goal of this study is determine the safety and feasibility of a conditioning region
consisting of non-myeloablative doses of busulfan and fludarabine prior to allo-stem cell
transplantation to treat patients with sickle cell disease and thalassemia major. By using
molecular assays of chimerism and detailed analysis of T cell function, the efficacy and
longer-term immunologic impact of the proposed treatment regimen can be assessed.
2004-2005
Nonmyelolablative allogeneic stem cell transplantation for treatment of severe
hemoglobinopathies
Brigham and Women’s Hospital Young Investigator Award
PI ($37,500)
The major goal of this study is to develop sensitive assays to measure lineage specific
chimerism that can be applied to monitoring response following nonmyeloablative allostem cell transplantation for the treatment of hemoglobinopathies.
2004-2006
GM-K562 vaccination for treatment of minimal residual disease in patients with chronic
myelogenous leukemia.
DFCI Dunkin’ Donuts Award for Outstanding Clinical Investigation
PI ($142,755)
The major goal of this study is to test the biologic effects of vaccination using irradiated
GM-K562 cells for the treatment of minimal residual disease in patients with chronic
myelogenous leukemia.
2005-2007
GM-CSF producing tumor cells as a chronic myelogenous leukemia vaccine.
NIH-NCI/R21 CA 115043-01
PI ($381,652)
The major goals of this study are to determine the safety and toxicity of irradiated GMK562 cell vaccination in chronic myelogenous leukemia patients, to determine its effects
on disease burden, and to characterize the immune activity of GM-K562 cells in chronic
myelogenous leukemia patients.
2006-2007
Parallel monitoring of antigen-specific humoral immunity following immune-based
therapy for chronic myelogenous leukemia
5
Dana-Farber Cancer Institute Fellowship, Eleanor and Miles Shore Program.
PI ($28,181)
The major goal of this study is to identify a set of reliable markers against which immunity
consistently develops following immune-based intervention for chronic myelogenous
leukemia, using large-scale serologic analysis
2006-2011
T cell immunity against novel leukemia antigens
Howard Hughes Medical Institute Physician-Scientist Early Career Award.
PI ($375,000)
The major goals of this study are identify to chronic myelogenous leukemia progenitor cell
associated antigens and to determine if they induce T and B cell responses following
vaccination with a cell-based chronic myelogenous leukemia vaccine
2007-2009
Toll-like receptor (TLR) activation in tumor immunity following allogeneic hematopoietic
stem cell transplantation
Claudia Adams Barr Program in Cancer Research
PI ($300,803)
The major goals of this study are to identify the specific leukemia-associated antigens that
form complexes with immunostimulatory nucleic acids to activate TLRs, identify the
immune cells that are stimulated by these complexes, and define the mechanism by which
immunity against these antigens can be initiated and enhanced following donor
lymphocyte infusion (DLI).
2007-2010
Immune-targeted leukemia antigens for eradication of chronic myelogenous leukemia stem
cells
Damon-Runyon Clinical Investigator Award.
PI ($300,000)
The major goals of this study are to advance our mechanistic understanding of the GvL
effect that can eradicate chronic myelogenous leukemia stem cells by identifying target
antigens in leukemia cells as well as innate mechanisms that initiate GvL.
2007-2010
Immune-targeted leukemia antigens for the immunotherapy of chronic lymphocytic
leukemia.
Leukemia and Lymphoma Society Translational Research Program Award
PI ($540,540)
The major goals of this study are to characterize expression of chronic lymphocyticassociated donor lymphocyte infusion antigens, and analyze the serologic and T cell
responses developing against them in the donor lymphocyte infusion setting.
2008-2009
Defining personal tumor-specific neoantigens for induction of anti-tumor immunity
SPARC award, Broad Institute
Co-PI ($146,004)
The major goal of this study is to undertake whole genome and exome sequencing of
tumors to define genetic alterations that could be targeted immunologically.
2008-2010
GM-CSF secreting tumor cell vaccines to enhance post-transplant anti-chronic
6
lymphocytic leukemia immunity
NIH-NCI/R21 CA132232-01
PI ($442,526)
The major goals of this study are to determine the feasibility, safety, and toxicity of
administering a vaccine consisting of irradiated autologous tumor cells admixed with GMK562 cells following reduced intensity transplantation in patients with advanced chronic
lymphocytic leukemia. This study will determine if tumor/GM-K562 vaccination in
transplanted chronic lymphocytic leukemia patients stimulates antigen-specific B and T
cell immunity.
2010-2012
Developing adoptive cellular therapy for the treatment of chronic lymphocytic leukemia
Damon-Runyon Cancer Research Foundation Clinical Investigator Award
PI ($250,000)
The major goals of this study are to determine whether post-transplant cellular vaccines
consistently induce expansion of chronic lymphocytic leukemia-specific donor T cells in
patients and whether chronic lymphocytic leukemia-reactive T cells also be expanded from
naïve normal donors.
Current
2010-2014
Post-transplant vaccines to enhance graft-versus-leukemia responses
NIH-NHLBI/1RO1HL103532-01
PI ($1,000,000)
The major goals of this study are to determine if cell-based vaccination enhances immune
reconstitution and enhances donor T cell reactivity against chronic lymphocytic leukemiarestricted antigens relative to broadly-expressed self antigens; and whether target antigens
of CD8+ T cells induced by post-transplant chronic lymphocytic leukemia vaccines can be
identified
2011-2013
Clinical and biologic activity of whole chronic lymphocytic leukemia-based posttransplant vaccines
Leukemia and Lymphoma Society Translational Research Program Award
PI ($360,000)
The major goal of this study is to define the clinical efficacy of vaccination in this phase
I/II study of patients with advanced chronic lymphocytic leukemia, and to determine if
patients following vaccination develop chronic lymphocytic leukemia-specific antibody
responses
2011-2014
Coupled genetic and functional dissection of chronic lymphocytic leukemia
American Association for Cancer Research SU2C Innovative Research Grant
PI ($681,818)
The major goals of this study are to select candidate genes and pathways that drive chronic
lymphocytic leukemia, assess the value of driver mutations and their expression in
predicting clinical outcomes, and define the functional effects of genetically altered genes
and pathways
7
2011-2014
Hematopoietic cell therapy for young adults with sickle cell disease
1R34 HL 108761-01 (Krishnamurti, Lakshmanan)
Investigator
The major goal of this study is to determine the feasibility and tolerability of hematopoietic
stem cell transplantation in young adults with sickle cell disease, and measure the impact
of donor hematopoiesis on end-organ function
2011-2016
Personal tumor antigens for immunity against chronic lymphocytic leukemia
NIH-NCI/1R01CA155010-01A1
PI ($1,037,500)
The major goals of this study are to determine whether the genes with somatic mutations in
chronic lymphocytic leukemia patients generate mutated peptides that elicit T cell
responses that are lytic to leukemia cells.
2012-2014
The role of mutations in RNA splicing pathway genes in chronic lymphocytic leukemia
Lymphoma Research Foundation
PI ($250,000)
The major goals of this study are to determine the mechanisms by which mutations in the
RNA splicing pathway contribute to pathogenesis of chronic lymphocytic leukemia
2012-2015
Targeting the spliceosome in CLL
Leukemia Lymphoma Society
PI ($540,054)
The major goals of this study are to determine effects of the spliceosome inhibitors on
RNA splicing in primary CLL cells and in a mouse model of CLL.
2012-2017
The role of the SF3B1 splicing factor in chronic lymphocytic leukemia
NIH/R01HL116452-01
PI
The major goals of this study are to define the mechanisms by which mutated SF3B1
promotes leukemogenesis in CLL.
Current Unfunded Projects
2000-
Co-Investigator, Protocol 00-159. Donation of Blood Cells for Examination of Immune
Function
This protocol seeks the collection of peripheral blood mononuclear cells from adult
volunteers by research leukapheresis for research studies of immune function.
8
2004-
Co-Investigator, Protocol 04-126. GM-K562 + Gleevec in chronic myelogenous leukemia
CML.
I conceived and designed this protocol, which seeks to assess the safety and biologic
activity of vaccinating chronic myelogenous leukemia patients with persistent residual
disease on Gleevec with a vaccine consisting of irradiated K562 cells (a chronic
myelogenous leukemia cell line), that has been engineered to secrete the cytokine adjuvant
GM-CSF.
2006-
Principal Investigator, Protocol 06-196. Reduced intensity stem cell transplantation for
advanced chronic lymphocytic leukemia followed by vaccination with lethally irradiated
autologous tumor cells admixed with granulocyte macrophage-colony stimulating factor
secreting K562 cells.
I conceived and designed this protocol, which seeks to assess the safety and toxicity of
vaccination with irradiated autologous tumor cells admixed with irradiated bystander
cells secreting the cytokine adjuvant GM-K562 cells, which is administered in the early
post-allogeneic transplant period following reduced intensity conditioning for chronic
lymphocytic leukemia patients with advanced disease. I have enrolled and been treating
physician for a number of patients on this study.
2006-
Principal Investigator, Protocol 06-200. Banking of chronic lymphocytic leukemia tumor
cells for vaccine generation.
I conceived and designed this protocol, which seeks to bank tumor cells from patients with
advanced chronic lymphocytic leukemia CLL, collected by marrow biopsy, lymph node
biopsy or from venipuncture. I have been responsible for undertaking informed consent for
a number of patients on this study, as well as marrow harvest of tumor cells.
2009-
Principal Investigator, Protocol 09-013. Whole Genome Sequencing to Discover Personal
Tumor Neoantigens.
This study seeks to request permission from cancer patients for whole genome analysis of
their tumors, including sequencing. In addition to conceiving and designing this protocol,
I have undertaken informed consent with several subjects of this study.
Report of Local Teaching and Training
Teaching of Students in Courses
1996
1997
Didactic and bedside teaching of topics in
Internal Medicine
Harvard Medical School
Third year (10 medical students) and fourth
year (6 medical students)
Daily M-F for one month
Physical examination in Hematology
Second year medical students
Harvard Medical School
½ day per semester
9
2003-
2012
HST 160 (Molecular Biology and Genetics
in Modern Medicine)
1-4th year medical, PhD or M/PhD students
Harvard Medical School
2 students per year, 40 hours per student for
discussion and instruction
BIO312 (Consultation)
Harvard School of Public Health
2nd-4th years doctoral biostatistics students
3 hours per semester
(12 students)
Formal Teaching of Residents, Clinical Fellows and Research Fellows (post-docs)
2009Introduction to Basic Science Lecture Series Dana-Farber/Partners CancerCare
1st year Clinical Fellows, Medical Oncology 1 hour lecture
Clinical Supervisory and Training Responsibilities.
2000-
Inpatient Blood and Marrow Transplant
Service, Brigham and Women’s Hospital
4 weeks per year
2000-
Inpatient consult attending, Hematologic
Malignancies, Brigham and Women’s
Hospital
4 weeks per year
Laboratory and Other Research Supervisory and Training Responsibilities
2004-
Supervise 10 post-doctoral fellows, 4
medical students and 4 research
assistants/ DFCI
Daily mentorship for 8 years
Formally Supervised Trainees and Faculty
2004-2006
Yun Lin, MD PhD/ Associate Scientist, Temple University, Philadelphia, PA
First author on article in JCI; ASH Abstract Achievement and Travel Award, 2006
2006-2007
Ovidiu Marina, MD/ PGY-3, Resident in Radiation Oncology, William Beaumont
Hospital, Royal Oak, MI
HHMI-funded Medical Student Research Fellow (Case Western Reserve Medical School)
First author on articles in J Prot Res, Cancer Res, and Methods in Mol Biol and
Recipient of HHMI Medical Student Research Fellowship
ASH Abstract Achievement and Travel Award, 2007
2007-2008
Melinda Biernacki, MD/ PGY-3, Resident in Medicine & Pediatrics, Brown
University/Lifespan Hospitals, Providence, RI
5 year Honors Medical Student Research Fellow (University of Connecticut Medical
10
School); ASH Abstract Achievement and Travel Award, 2008
First author on articles in Cancer Res and Blood; co-author on papers in Blood, Biol BMT,
Can Res, J Prot Res, Br J Haematol, Exp Hem.
2007-2012
Ann X. Cai, MD / Intern in Medicine, UCSF
HHMI-funded Medical Student Research Fellow (HMS)
Recipient of the Proctor Foundation Scholarship
ASH Abstract Achievement and Travel Award recipient, 2010
Co-author on 3 papers in Cancer Research and JCI
Lead author of an article in Clinical Cancer Research
2008-2010
Ursula Hainz, PhD / Post-doctoral research fellow, Children’s Cancer Research Institute,
Vienna, Austria
American Society for Blood and Marrow Transplantation Travel award, 2010
Co-author on article in Can Research, Cancer Immunotherapy Immunology
2008-
Lili Wang, MD PhD/ Post-doctoral research fellow
Co-first author on article in NEJM, co-author on article in Cell
ASH Abstract Achievement and Travel Award 2010, 2011, 2012
Recipient of Lymphoma Research Foundation Postdoctoral Award 2013
2008-2010
Li Zhang, PhD/ Associate Professor, West China Hospital, Sichuan University
Co-first author on article in JCI; co-author on article in NEJM
2009
Ana M. Brusic, MBBS, BMedSc / Intern, Eastern Health Hospital Group, Melbourne,
Victoria
Honours/First Class Masters research thesis, Monash University, Australia
Lead author of an article in Oncoimmunology
2009-2011
Quinlan Sievers /2nd year MD-PhD student, Harvard Medical School
Co-author on article in NEJM
2009-
Mohini Rajasagi, PhD / Post-doctoral research fellow
Co-author on an manuscript to Cancer Immunotherapy, Immunology
ASH Abstract Achievement and Travel Award 2012
2010-
Youzhong Wan, PhD / Post-doctoral research fellow
Co-first author on article in NEJM
ASH Abstract Achievement and Travel Award, 2011
Recipient of Leukemia and Lymphoma Society Postdoctoral Award, 2012
2010-2012
Masayasu Naito, MD PhD / Assistant Professor, Department of Gastroenterological
Surgery, Fukuoka University School of Medicine, Japan
ASH Abstract Achievement and Travel Award, 2011
Lead author of an manuscript in Cancer Immunotherapy, Immunology
11
2011-
Ute M. Burkhardt, PhD/ Post-doctoral research fellow
Oral abstract presenter at ASBMT, 2012
Co-author on an in press manuscript to Cancer Immunotherapy, Immunology
Lead author of a manuscript under review at Journal of Clinical Investigation
Abstract achievement award, NCI-Relapse Workshop 2012
2011-
Dan-Avi Landau, MD/ Post-doctoral research fellow
American Society of Hematology Abstract Achievement Award, 2011; Recipient of a 2011
American Society of Hematology Research Training Award for Fellows
Recipient of American Cancer Society Postdoctoral Fellowship, 2012
Lead author of a paper in Cell, 2013
Plenary abstract session speaker at the 2012 Annual American Society of Hematology
meeting
2012-
Jintaek Kim, PhD/Post-doctoral research fellow
Local Invited Presentations
No presentations below were sponsored by outside entities.
2001
Identification of antigen targets of the graft-versus-leukemia response/ Immunology
Seminar Series
Harvard Institutes of Medicine, Harvard Medical School
2002
Dissecting the graft-versus-leukemia effect: identification of target antigens / Grand
Rounds
Division of Blood and Marrow Transplantation (BMT), Harvard Medical School
2002
Nonmyeloablative allogeneic stem cell transplantation for severe hemoglobinopathies /
Hematology Seminar Series
Division of Hematology, Brigham and Women’s Hospital
2003
Nonmyeloablative allogeneic stem cell transplantation for severe hemoglobinopathies /
Hematology Seminar Series
Division of Hematology, Brigham and Women’s Hospital
2004
Nonmyeloablative allogeneic stem cell transplantation for severe hemoglobinopathies /
Grand Rounds
BMT, Harvard Medical School
2004
Stem cell therapy for hemoglobinopathies / Clinical Pathology Seminar Series
Brigham and Women’s Hospital, Harvard Medical School
2005
Stem cell transplantation for sickle cell anemia/ BWH Medicine-Pathology Conference
Brigham and Women’s Hospital, Harvard Medical School
12
2006
Cellular vaccines for chronic myelogenous leukemia / Joint Immunology Research
Seminar
DFCI-BWH-JDC, Harvard Medical School
2006
Cellular vaccines for chronic myelogenous leukemia / Cancer Immunology Seminar Series
Dana-Farber Cancer Institute, Harvard Medical School
2007
Identification of antigen targets of the graft-versus-leukemia response/ Immunology
Seminar Series
Harvard Institutes of Medicine, Harvard Medical School
2007
Dissecting the GvL response—identification and characterization of target antigens/ Grand
Rounds
BMT, Harvard Medical School
2007
Nonmyeloablative allogeneic stem cell transplantation for severe
hemoglobinopathies/Hematology Seminar Series
Division of Hematology, Brigham and Women’s Hospital
2007
Monitoring of erythroid-lineage specific engraftment following transplantation for
hemoglobinopathies / Transfusion Medicine Grand Rounds
Harvard Medical School
2008
Molecular monitoring of lineage specific chimerism / Clinical Pathology Grand Rounds
Brigham and Women’s Hospital, Harvard Medical School
2009
Marrow hematopoietic progenitors as chronic lymphocytic leukemia-initiating cells /
Seminar Series Lecture
MGH Cancer Center, Harvard Medical School
2010
Dissecting and enhancing immunity against leukemia / Grand Rounds
MGH Cancer Center, Harvard Medical School
2010
Dissecting and enhancing immunity against chronic lymphocytic leukemia / Retreat
speaker
Lymphoma and Myeloma Retreat, DFCI
2010
Developing novel immunotherapy for chronic lymphocytic leukemia and understanding
chronic lymphocytic leukemia biology/Invited speaker
Broad Institute, Cambridge, MA
2010
Whole tumor cell based vaccines to enhance immunity against chronic lymphocytic
leukemia / Grand Rounds
Bone Marrow Ttransplantation, Harvard Medical School
13
2011
Discovery of driver mutations in chronic lymphocytic leukemia / Speaker
Broad Institute Cancer Genome Working Group, Cambridge, MA
2011
Discovery of driver mutations and pathways in chronic lymphocytic leukemia based on
whole genome and exome sequencing/ Hematologic Neoplasia Division Seminar
DFCI
2011
Whole tumor cell based vaccines to enhance immunity against chronic lymphocytic
leukemia / Hematologic Neoplasia Division Seminar
DFCI
2011
Discovery of driver mutations in chronic lymphocytic leukemia / Cancer Program Seminar
Series
Broad Institute, Cambridge, MA
2011
Large-scale genome analysis of chronic lymphocytic leukemia reveals novel cancer genes
including SF3B1/ Hematologic Neoplasia Division Seminar
DFCI
2011
Discovery of personal neoantigens/ Cancer Program Seminar Series
Broad Institute
2012
Understanding the role of mutated SF3B1 in CLL/ Cancer Program Seminar Series
Broad Institute
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia / Invited
speaker
Barr Presidential Advisory Committee, DFCI
2012
Developing a personalized neoantigen cancer vaccine/ Invited speaker
Broad Institute Cancer Genome Workshop seminar series
2012
Tumor heterogeneity in CLL: detection and implications/Invited speaker, Single Cell
Genomics Collaborative Special Seminar
Broad Institute, Cambridge MA
2012
Developing a personalized neoantigen cancer vaccine/Invited speaker
Broad Institute Annual Retreat, Harvard Medical School, Boston
2013
Developing a personalized neoantigen cancer vaccine/Invited speaker
DFHCC AML Retreat, Beth Israel/Deaconess Hospital, Boston
2013
Evolution and impact of subclonal mutations in CLL/ Invited speaker
Leukemia Research Conference/Massachusetts General Hospital, Boston
2013
Developing a personalized neoantigen cancer vaccine/Invited speaker
14
Broad Institute Cancer Biology seminar series/Cambridge MA
Report of Regional, National and International Invited Teaching
and Presentations
Invited Presentations and Courses
No presentations below were sponsored by outside entities.
Regional
2004
Nonmyeloablative allogeneic stem cell transplantation for severe
hemoglobinopathies/Invited speaker
Department of Hematology, Boston University Medical Center, Boston MA
2007
Cellular vaccines for the treatment of CLL/Symposium on Advances in Chronic
Lymphocytic Leukemia
Tufts-New England Medical Center, Boston, MA
2007
Hematopoietic allogeneic stem cell transplant for severe hemoglobinopathies/ Grand
Rounds
Hematology-Oncology, University of Connecticut School of Medicine, Farmington, CT
2011
From graft-versus-leukemia to effective cancer vaccines/ Keynote speaker and panel
discussant
HHMI Northeast Regional Medical Fellows Program, Boston MA
2012
Tumor immunity and cancer genomics/ Discussion leader
Broad Institute Cancer Program Retreat, Chatham MA
2013
Clonal heterogeneity in CLL: Immunotherapeutic implications/invited speaker
Pathology Seminar Series
Boston University School of Medicine Department of Pathology and Laboratory Medicine,
Boston MA
National
1998
Reconstitution of T cell receptor repertoire diversity following allogeneic bone marrow
transplantation is related to hematopoietic chimerism / Abstract presenter
American Society of Hematology Annual Meeting, Miami, FL
1999
Serologic identification of antigens associated with response to donor lymphocyte infusion
(DLI) for relapsed CML after allogeneic BMT/ Abstract presenter
American Society of Hematology Annual Meeting, New Orleans, LA
15
2002
CML28 and CML66 are GVL-associated antigens that are overexpressed in malignant
hematopoietic tissue/ Abstract presenter
American Society for Blood and Marrow Transplantation Annual Meeting, Orlando, FL
2003
Dissecting the Graft-versus-Leukemia Effect: Identification of Target Antigens/ Invited
Speaker
Stanford University School of Medicine, Stanford, CA
2004
Nonmyeloablative allogeneic stem cell transplantation for severe hemoglobinopathies/
Grand Rounds
Division of Hematology-Oncology, Louisiana State University at Shreveport, Shreveport,
LA
2005
Dissecting the graft-versus-leukemia effect: Identification of target antigens/ Invited
speaker
University of Michigan, Ann Arbor, MI
2005
Graft-versus-leukemia target antigens in chronic myelogenous leukemia (CML) are
expressed on myeloid progenitor cells/ Abstract presenter
5th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), Boston,
MA
2005
Nonmyeloablative allogeneic stem cell transplant for severe sickle cell anemia/Invited
speaker
Wayne State University, Detroit, MI
2006
Effective graft-versus-leukemia responses are associated with the presence of nucleic acidimmunoglobulin complexes that stimulate TLR8 and TLR9/ Abstract presenter
American Society of Hematology Annual Meeting, Orlando, FL
2010
Graft-versus-leukemia antigen CML66 elicits coordinated B and T cell immunity after
donor lymphocyte infusion/Abstract presenter
American Society for Blood and Marrow Transplantation Annual Meeting; Orlando, FL
2010
Safety and clinical efficacy of early vaccination after non-myeloablative transplant for
advanced chronic lymphocytic leukemia /Abstract presenter
American Society for Blood and Marrow Transplantation Annual meeting; Orlando, FL
2010
Dissecting and enhancing immunity against leukemia / Grand Rounds
Hematology/Oncology, Northwestern University, Chicago, IL
2011
Hematopoietic allogeneic stem cell transplantation for sickle cell disease/ Education
session speaker
American Society for Blood and Marrow Transplantation Annual Meeting, Honolulu, HI
2011
Early-post transplant whole tumor cell vaccination elicits anti-tumor T cell responses in
16
patients with advanced CLL/ Abstract presenter
American Society for Blood and Marrow Transplantation Annual Meeting; Honolulu, HI
2011
Large-scale CLL genome analysis reveals novel cancer genes, including SF3B1 / Invited
speaker
CLL Research Consortium meeting, San Diego, CA
2011
Large-scale CLL genome analysis reveals novel cancer genes, including SF3B1 / Invited
speaker
Second International CLL Research Colloqium, San Diego, CA
2012
Dissecting and enhancing immunity against leukemia/ Invited speaker
National Cancer Institute; Bethesda MD
2012
Mining the tumor genome for graft-versus-leukemia targets / Plenary session chair and
speaker
American Society of Blood and Marrow Transplantation, San Diego, CA
CLL Research Consortium meeting, San Diego, CA
2012
Developing effective immune therapy for the treatment of CLL / Invited speaker DamonRunyon Cancer Research Foundation Symposium, New York City NY
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia /
Invited speaker
AACR/SU2C symposium, Chicago IL
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia / Invited
speaker
Ohio State University Medical Center, Columbus OH
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia/ Invited
speaker, Grand Rounds
Vanderbilt Medical Center, Nashville TN
17
2012
Tumor Genomics: Biology and Implications for Cellular Therapies/Invited Speaker
2nd International Workshop on the Biology, Prevention and Treatment of Relapse after
Hematopoietic Stem Cell Transplantation, NCI/NIH, Bethesda MD
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia/ Invited
speaker, Leukemia Grand Rounds
University of Texas/MD Anderson Cancer Center, Houston TX
2012
Clonal evolution in CLL: Therapeutic implications/ Invited speaker
Alliance Leukemia Correlative Science Committee Meeting, Chicago IL
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia/ Invited
speaker, Leukemia Grand Rounds
LI Jewish Medical Center, Manhasset NY
2012
Clonal evolution in CLL: therapeutic implications/ Invited speaker, CLL Research
Consortium symposium; Atlanta GA
2012
Understanding the role of mutations in SF3B1 and splicing in CLL/ Invited speaker/
American Society of Hematology Scientific Education Program, Subcommittee on
Hematopoiesis/ Atlanta GA
2012
RNA Splicing in Normal and Malignant Hematopoiesis/ Invited speaker/ American
Society of Hematology Scientific Forum/ Atlanta GA
2013
Clonal heterogeneity in CLL: Therapeutic implications/Hematology-Oncology Grand
Rounds speaker
Memorial Sloan-Kettering Cancer Center, New York City, NY
2013
Clonal heterogeneity in CLL: Immunotherapeutic implications/invited speaker
University of California at San Diego, La Jolla CA
2013
Impact of subclonal mutations in CLL/Invited speaker/ American Society of Cancer
Research Annual meeting Scientific Education Session, Washington DC
2013
Intraclonal heterogeneity in CLL/Invited speaker/Stand Up to Cancer Special Session,
American Society of Cancer Research Annual meeting, Washington DC
2013
Coupled genetic and functional dissection of chronic lymphocytic leukemia/ Invited
Speaker/ CLL Research Consortium Retreat, San Diego CA
International
2005
Nonmyeloablative allogeneic stem cell transplant for severe sickle cell anemia/ Invited
speaker
18
King’s College, London, England
2011
Early-post transplant whole tumor cell vaccination elicits anti-tumor T cell responses in
patients with advanced CLL/ Abstract presenter
European Society for Blood and Marrow Transplantation, Paris, France
2011
Large-Scale CLL Genome Analysis Reveals Novel Cancer Genes, Including SF3B1/
Invited speaker / Joint NCI-Japan Society for Promotion of Science workshop on Cancer
Genomics, Kyoto, Japan
2012
Coupled genetic and functional dissection of chronic lymphocytic leukemia/
Invited speaker/ 8th International CLL Workshop, Salzburg, Austria
Report of Clinical Activities and Innovations
Current Licensure and Certification
1996
Massachusetts Medical License
1997
American Board of Internal Medicine Certificate
2001
American Board of Internal Medicine, Medical Oncology
2002,2012
American Board of Internal Medicine, Hematology
2012
American Board of Internal Medicine, Hematology
Practice Activities
2000- Inpatient Care
2000-
Ambulatory Care
Adult blood and marrow
transplantation, Brigham
and Women’s Hospital
Adult blood and marrow
transplantation, DFCI
4 weeks per year
½ session per week
Report of Technological and Other Scientific Innovations
Methods to detect
lineage-specific
cells.
U.S. Provisional Application Serial No. 60/506221, filed September 25,
2003, and U.S. Provisional Application Serial No. 60/509594, filed
October 8, 2003.
WU CJ, Ritz J, inventors.
As a member of the Ritz lab, I generated a molecular assay that uses
quantitative measurement of transcripts expressed uniquely in a particular
cell lineage as a marker to measure lineage-specific chimerism. This type
of assay is now being used in a number of national collaborative clinical
19
trials of allotransplantation of sickle cell disease to functionally assess
impact of transplantation.
Immunogenic tumor
antigens: nucleic
acids and
polypeptides
encoding the same
and methods of use
thereof.
US Patent Application 20363-006, filed 2002.
WU CJ, Yang XF, Ritz J, inventors.
As a member of the Ritz lab, I demonstrated that serologic approaches
could be utilized to rapidly identify the tumor antigens CML28 and
CML66 that could be targets of immunotherapy directed against CML.
Compositions and
US Patent Application: 13/108,610. Filed May 16, 2011
methods of
Hacohen N, WU CJ, inventors.
identifying tumorspecific neoantigens This application describes the application of genomic approaches to
identify genetic alterations that may elicit immunologic reactivity, derived
from tumors.
Report of Education of Patients and Service to the Community
No activities below were sponsored by outside entities.
2002
Allogeneic Stem Cell Transplantation for Sickle Cell Disease / Keynote
speaker; Boston Pan-African Medical Society Annual Meeting, Boston MA
2003
Current advances in the care of patients with sickle cell disease / Invited
speaker; Boston Community Sickle Cell Support Group, Boston MA
2004
Current advances in the care of patients with sickle cell disease./ Invited
speaker and panel discussant; Boston Community Sickle Cell Support
Group, Boston MA
Recognition
2004
Medical Service Award
Boston Community Sickle Cell Support
Group
Report of Scholarship
Peer reviewed publications in print or other media
•
Research investigations
20
1.
WU CJ, Karttunen JT, Chin DHL, Sen D, Gilbert W. Murine memory B cells are double isotype
expressors. Immunology 1991; 72: 48-55.
2.
WU CJ, Lovett M, Wong-Lee J, Moeller F, Kitamura M, Billingham ME, Starnes VA, Clayberger
C. Cytokine gene expression in rejecting cardiac allografts. Transplantation 1992; 54: 326-32.
3.
Whitehead BF, Stoehr C, WU CJ, Patterson G, Burchard EG, Theodore J, Clayberger C, Starnes
VA. Cytokine gene expression in human lung transplant recipients. Transplantation 1993; 56:95661.
4.
WU CJ, Kurbegov D, Lattin B, Burchard EG, Valantine H, Billingham ME, Starnes VA, Clayberger
C. Cytokine gene expression in human cardiac allograft recipients. Transplant Immunology 1994;
2: 199-207.
5.
WU CJ, Vasconcelles M, DePiro P, Van den Abbeele A, Rakusin A, Bechard K, Skarin A. Primary
cardiac angiosarcoma presenting as a malignant pericardial effusion. J Clin Oncol 1998; 16: 39135.
6.
WU CJ, Scadden D. Posttransplant Kaposi's sarcoma treated with paclitaxel. J Clin Oncol 1998;
16: 3478-9.
7.
WU CJ, Alyea EP, Chillemi A, Neuberg D, Soiffer R, Ritz J. Reconstitution of T cell receptor
repertoire diversity following allogeneic bone marrow transplantation is related to hematopoietic
chimerism. Blood 2000; 95: 352-9.
8.
WU CJ, Yang XF, McLaughlin S, Neuberg D, Canning C, Stein B, Alyea EP, Soiffer RJ, Dranoff
G, Ritz J. Detection of a potent humoral response associated with immune-induced remission of
chronic myelogenous leukemia. J Clin Invest 2000; 106: 705-14.
9.
Yang XF, WU CJ, McLaughlin S, Chillemi A, Wang KS, Canning C, Alyea EP, Kantoff P, Soiffer
RJ, Dranoff G, Ritz J. CML66, a novel broadly immunogenic tumor antigen elicits a humoral
immune response associated with remission of chronic myelogenous leukemia. Proc Natl Acad Sci
USA 2001; 98: 7492-7.
10. Hochberg EP, Chillemi AC, WU CJ, Neuberg D, Canning C, Hartman K, Alyea EP, Soiffer RJ,
Kalams SA, Ritz J. Quantitation of T cell neogenesis in vivo after allogeneic bone marrow
transplantation in adults. Blood 2001; 98: 1116-21.
11. Zorn E, Orsini E, WU CJ, Stein B, Chillemi A, Canning C, Alyea EP, Soiffer RJ, Ritz J (1). A
CD4+ T cell clone selected from a CML patient after donor lymphocyte infusion recognizes BCRABL breakpoint peptides but not tumor cells. Transplantation 2001; 71: 1131-7.
12. Bellucci R, Alyea EP, Weller E, Chillemi A, Hochberg E, WU CJ, Canning C, Schlossman R,
Soiffer RJ, Anderson KC, Ritz J. Immunologic effects of prophylactic donor lymphocyte infusion
after allogeneic marrow transplantation for multiple myeloma. Blood 2002; 99: 4610-7.
21
13. Soiffer RJ, Alyea EP, Hochberg E, WU C, Canning C, Parikh B, Zahrieh D, Webb I, Antin J, Ritz J.
Randomized trial of CD8+ T-cell depletion in the prevention of graft-versus-host disease associated
with donor lymphocyte infusion. Biol Blood Marrow Transplant 2002: 8: 625-32.
14. Yang XF*, WU CJ*, Chen LY, Alyea EP, Canning C, Kantoff P, Soiffer RJ, Dranoff G, Ritz J.
CML28 is a broadly immunogenic antigen which is overexpressed in tumor cells. Cancer Res 2002:
62: 5517-22. (* denotes equal contributors)
15. WU CJ, Neuberg D, Chillemi A, McLaughlin S, Hochberg EP, Galinsky I, DeAngelo D, Soiffer R,
Alyea EP, Capdeville R, Stone RM, Ritz J. Quantitative monitoring of BCR/ABL transcript during
STI-571 therapy. Leuk Lymph 2002; 43:2281-9.
16. WU CJ, Hochberg EP, Rogers SA, Biernacki M, Nascimento A, Kutok JL, Marks P, Bridges KR,
Ritz J. Molecular assessment of erythroid lineage chimerism following non-myeloablative
allogeneic stem cell transplantation. Exp Hematol 2003; 31: 924-33.
17. Antin JH, Kim HT, Cutler C, Ho VT, Lee SJ, Miklos DB, Hochberg EP, WU CJ, Alyea EP, Soiffer
RJ (1). Sirolimus, tacrolimus and low-dose methotrexate for graft-versus-host disease prophylaxis
in mismatched related donor or unrelated donor transplant. Blood 2003; 102: 1601-5.
18. Yan Y, Phan L, Yang F, Talpaz M, Yang Y, Xiong Z, Ng B, Timchenko NA, WU CJ, Ritz J, Wang
H, Yang XF. A novel mechanism of alternative promoter and splicing regulates the epitope
generation of tumor antigen CML66-L. J Immunol 2004; 172: 651-60.
19. Srinivasan J, WU CJ, Amato A. Inflammatory myopathy associated with imatinib meslyate therapy.
J Clin Neuromusc Dis 2004; 5: 119-21.
20. Bellucci R, WU CJ, Chiaretti S, Weller E, Davies FE, Alyea EP, Dranoff G, Anderson KC, Munshi
NC, Ritz J. Complete response to donor lymphocyte infusion in multiple myeloma is associated
with antibody responses to highly expressed antigens. Blood 2004; 103: 656-63.
21. Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ, Hochberg EP, WU CJ, Alyea EP, Cutler
C, Ho V, Soiffer RJ, Antin JH, Ritz J. Antibody responses to H-Y minor histocompatibility
antigens correlate with chronic graft versus host disease and disease remission. Blood 2005; 105:
2973-8.
22. Bellucci R, Alyea EP, Chiaretti S, WU CJ, Zorn E, Weller E, WU B, Canning C, Schlossman R,
Munshi NC, Anderson KC, Ritz J. Graft-versus-tumor response in patients with multiple myeloma
is associated with antibody response to BCMA, a plasma cell membrane receptor. Blood 2005;
105:3945-50.
23. WU CJ, Biernacki M, Kutok JL, Rogers S, Chen LY, Yang XF, Soiffer RJ, Ritz J. Graft-versusleukemia target antigens in chronic myelogenous leukemia (CML) are expressed on myeloid
progenitor cells. Clin Cancer Res 2005; 11: 4504-11.
24. WU CJ, Krishnamurti L, Kutok JL, Biernacki M, Rogers S, Zhang W, Antin JH, Ritz J. Evidence
22
for ineffective erythropoiesis in severe sickle cell disease. Blood 2005; 106: 3639-45.
25. WU CJ, Gladwin M, Tisdale J, Hsieh M, Biernacki M, Rogers S, Wang X, Walters M, Zahrieh D,
Antin JH, Ritz J, Krishnamurti L. Mixed hematopoietic chimerism for sickle cell disease prevents
intravascular hemolysis. Br J Haematol 2007; 139: 504-7.
26. Nardi V, Raz T, Cao X, WU CJ, Stone R, Cortes J, Deininger M, Church G, Zhu J, Daley GQ (2).
Quantitative monitoring by polymerase colony assay of known mutations resistant to ABL kinase
inhibitors. Oncogene 2008; 27: 775-82.
27. Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rhostami S, Zhang W,
Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, WU CJ. Erythroid-lineage specific
engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell
transplantation. Exp Hematol 2008; 36: 1205-15.
28. Krishnamurti L, Kharbanda S, Biernacki MA, Zhang W, Baker SB, Wagner JE, WU CJ. Stable long
term donor engraftment following reduced intensity hematopoietic cell transplantation for sickle cell
disease. Biol BMT 2008; 14:1270-8.
29. Marina O, Biernacki MA, Brusic V, WU CJ. A concentration-dependent analysis method for highdensity protein microarray. J Prot Res 2008; 7: 2059-68.
30. Jagani Z, Song K, Kutok JL, Dewar MR, Melet A, Santos T, Grassian A, Ghaffari S, WU C,
Yeckes-Rodin H, Ren R, Miller K, Khosravi-Far R. Proteasome inhibition causes regression of
leukemia and abrogates BCR-ABL- induced evasion of apoptosis in part through regulation of
forkhead tumor suppressors. Cancer Res 2009; 69:6546-55.
31. Ofran Y, Kim HS, Brusic V, Blake L, Mandrell M, WU CJ, Sarantopoulos S, Bellucci R, Keskin
DB, Soiffer RJ, Antin JH, Ritz J. Diverse patterns of T cell response against multiple newly
identified human Y chromosome encoded minor histocompatibility epitopes. Clin Cancer Res 2010;
16:1642-51.
32. Weisberg E, Choi HW, Ray A, Barrett R, Zhang JM, Sim T, Zhou WJ, Seelinger M, Cameron M,
Azam M, Mayeda M, Moreno D, Kung AL, Janne PA, Khosravi-Far R, Melo J, Manley PW,
Adamia S, WU C, Gray N, Griffin JD. Discovery of a small molecule type II inhibitor of wild-type
and gatekeeper mutants of BCR-ABL, PDGFRĄ, Kit, and Src kinases. Blood 2010; 115:4206-16.
33. Biernacki MA, Marina O, Zhang W, Liu FL, Bruns I, Cai A, Zhang W, Neuberg D, Canning CM,
Alyea EP, Soiffer RJ, Brusic V, Ritz J, WU CJ. Antigen targets of remission-inducing immune
therapy are expressed on CML progenitor cells. Cancer Res 2010; 70:906-15.
34. Zhang W, Choi JW, Zeng WY, Rogers SA, Alyea EP, Rheinwald JG, Canning CM, Brusic V,
Sasada T, Reinherz EL, Ritz J, Soiffer RJ, WU CJ. Graft-versus-leukemia antigen CML66 elicits
coordinated B and T cell immunity after donor lymphocyte infusion. Clin Cancer Res 2010;
16:2729-39.
23
35. Marina O, Hainz U, Biernacki MA, Zhang W, Cai A, Duke-Cohan JS, Liu FL, Brusic V, Neuberg D,
Kutok JL, Alyea EP, Canning CM, Soiffer RJ, Ritz J, WU CJ. Serologic markers of effective
tumor immunity against chronic lymphocytic leukemia include non-mutated B cell antigens. Cancer
Res 2010; 70:1344-55.
36. Koreth J, Biernacki M, Aldridge J, Kim HT, Alyea EP, Armand P, Cutler C, Ho VT, WU CJ, Antin
JH, Soiffer RJ. Syngeneic donor hematopoietic stem cell transplantation is associated with high
rates of engraftment syndrome. Biol Blood Marrow Transplant 2011; 17: 421-8.
37. Anderson KS*, Zeng WY*, Sasada T*, Choi JW, Riemer AB, Su M, Drakoulakos D, Kang YJ,
Brusic V, WU CJ, Reinherz EL. Impaired tumor antigen processing by immunoproteasomeexpressing CD40-activated B cells and dendritic cells. Cancer Immunol Immunotherapy 2011;
60:857-67. (*denotes equal contributors)
38. Lin Y*, Zhang L*, Cai AX, Lee M, Zhang W, Neuberg D, Canning CM, Soiffer RJ, Alyea AP, Ritz
J, Hacohen N, Means TK, WU CJ. Effective post-transplant anti-tumor immunity is associated
with TLR-stimulating nucleic acid-immunoglobulin complexes in humans. J Clin Invest 2011;
121:1574-84. (* denotes equal contributors)
39. Huynh HD, Zheng JK, Umikawa M, Silvany R, Xie XJ, WU CJ, Holzenberger M, Wang QM, and
Zhang CC. Components of the hematopoietic compartments in tumor stroma and tumor-bearing
mice. PLoS ONE 2011; 6: e18054
40. Wang L*, Lawrence MS*, Wan YZ* Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko
A, Deluca DS, Zhang L, Zhang W, Vartanov A, Fernandes SM, Goldstein NR, Folco EG, Cibulskis
K, Tesar B, Sievers QL, Shefler E, Gabriel S, Hacohen N, Reed R, Meyerson M, Golub TR, Lander
ES, Neuberg D, Brown JR*, Getz G*, WU CJ*. Sequencing of chronic lymphocytic leukemia
reveals frequent mutations in SF3B1, a component of the spliceosome. N Engl J Med
2011;365(26):2497-506 (* denotes equal contributors)
41. Biernacki MA, Tai YT, Zhang GL, Alonso A, Zhang W, Prabhala R, Zhang L, Munshi N, Neuberg
D, Soiffer RJ, Ritz J, Alyea EP, Brusic V, Anderson KC, WU CJ. Novel myeloma-associated
antigens revealed in the context of syngeneic hematopoietic stem cell transplantation. Blood 2012
119(13):3142-50.
42. Brown JR, Hanna M, Tesar B, Pochet N, Vartanov A, Fernandes SM, Werner L, Ash M, Roden CA,
MacConaill L, Hainz U, Longtine J, Wang YE, Correll M, Van De Peer Y, Regev A, WU CJ,
Neuberg D, Freedman AS. Germline copy number variation associated with Mendelian inheritance
of CLL in two families. Leukemia 2012; 26(7): 1710-3.
43. Brown JR, Hanna M, Tesar B, Werner L, Pochet N, Asara JM, Wang YE, Dal Cin P, Fernandes S,
Thompson C, Macconaill LE, WU CJ, Van de Peer Y, Correll M, Regev A, Neuberg D, Freedman
AS. Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic
lymphocytic leukemia. Clin Cancer Res. 2012;18 (4): 3791-3802
44. Brusic A, Hainz U, Wadleigh M, Neuberg D, Su M, Canning CM, DeAngelo D, Stone RM, Ritz J
24
Dranoff G, Sasada T, WU CJ. Detecting T-cell reactivity to whole cell vaccines: proof of concept
analysis of T-cell response to K562 cell antigens in CML patients. Oncoimmunology 2012 1:7; 1-9
45. Cai A, Keskin DB, Deluca DS, Alonso A, Zhang W, Zhang GL, Hammond NN, Nardi V, Stone RM,
Neuberg D, Sidney J, Brusic V, WU CJ. Mutated BCR-ABL generates immunogenic T cell
epitopes in CML Patients. Clin Cancer Res 2012; 18(20):5761-72
46.
Brown JR, Kim HT, Armand A, Cutler C, Fisher DC, Ho V, Koreth J, Ritz J, WU CJ, Antin,JH,
Soiffer RJ, Gribben JG, Alyea EP. Long-term follow-up of reduced intensity allogeneic stem cell
transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome Leukemia
2012;Aug 14 [Epub ahead of print].
47. Naito M, Hainz U, Fu BY, Stevenson KE, Burkhardt U, Ahove DA, Rajasagi M, Zhu BG, Alonso A,
Witten E, Matsuoka KI Neuberg D, Duke-Cohan J, WU CJ* and Freeman G*. CD40L-Tri, a novel
formulation of recombinant human CD40L that effectively activates B cells (* denotes equal
contributors) Cancer Immunotherapy, Immunology 2012 Aug 25 [Epub ahead of print].
48. Davids MS, Deng J, Wiestner A, Lannutti BJ, Wang L, WU CJ, Wilson WH, Brown JR, Letai A.
Decreased mitochondrial apoptotic priming underlies stroma-mediated treatment resistance in
chronic lymphocytic leukemia, Blood 2012; 120(17): 3501-9.
49. Shalek AK, Gaublomme JT, Wang L, Yosef N, Chevrier N, Andersen MS, Robinson JT, Pochet N,
Neuberg D, Gertner RS, Amit I, Brown JR, Hacohen N, Regev A, WU CJ, Park H. Nanowiremediated delivery enables functional interrogation of primary immune cells: application to the
analysis of chronic lymphocytic leukemia. Nano Lett. 2012 Dec 12;12(12):6498-504.
50. Landau DA*, Carter SL*, Stojanov P*, McKenna A, Stevenson K, Lawrence MS, Sougnez C,
Stewart C, Sivachenko A, Wang L, Wan YZ, Zhang W, Shukla SA, Vartanov A, Fernandes SM,
Saksena G, Cibulskis K, Tesar B, Gabriel S, Hacohen N, Meyerson M, Lander ES, Neuberg D,
Brown JR, Getz G*, WU CJ* Evolution and impact of subclonal mutations in chronic lymphocytic
leukemia. Cell 2013; 152(4):714-26.
51. Burkhardt UE, Hainz U, Stevenson K, Goldstein NR, Pasek M, Naito M, Wu D, Ho VT. Alonso A,
Hammond NN, Wong J, Sievers QL, Brusic A, McDonough SM, Zeng WY, Perrin A, Brown JR,
Canning CM, Koreth J, Cutler C, Armand P, Neuberg D, Lee JS. Antin JH. Mulligan RC, Sasada T,
Ritz J, Soiffer RJ, Dranoff G, Alyea EP, WU CJ. Autologous CLL cell vaccination early after
transplant induces leukemia-specific T-cells. Journal of Clinical Investigation (in press)
•
Other peer-reviewed publications
1. WU CJ. Immunologic targeting of the cancer stem cell. In: Girard, L, editor. The Stem Book.
Cambridge,
MA:
Harvard
Stem
Cell
Institute,
Harvard
University;
2008
(http://www.stembook.org).
25
Non-peer reviewed scientific or medical publications/materials in print or other media
•
Proceedings of meetings or other non-peer-reviewed research publications
1. Bellucci R, WU CJ, Chiaretti S, Alyea EP, Munshi NC, Ritz J. Antibody response to BCMA in
patients with multiple myeloma. Proceedings of the 12th International Congress of Immunology
and 4th Annual Conference of FOCIS; 2004 July 18-23; Montreal, Canada. Malden, MA: Wiley:
2004.
2. Gress RE, Miller JS, Battiwalla M, Hardy NM, Landau DA, WU CJ. Proceedings from the 2nd
NCI International Workshop on the Biology, Prevention and Treatment of Relapse after
Hematopoietic Stem Cell Transplantation: Report from the Committee on Biology of Relapse after
Transplantation; 2012 Nov 12-13; Bethesda MD
•
Reviews, chapters, monographs and editorials
1.
WU CJ, Ritz J. The immunocompromised host. In: Austen FR, editor. Samter's Immunologic
Diseases, 6th ed. Boston: Little, Brown and Company; 200l. p. 1067-85.
2.
WU CJ, Ritz J. The induction of tumor immunity following allogeneic stem cell transplantation. In:
Dranoff, G and Alt, F: editors. Advances in Immunology. Amsterdam: Elsevier; 2006. p. 129169.
3.
Brusic V, Marina O, WU CJ, Reinherz EL. Proteome informatics for cancer research: From
molecules to clinic. Proteomics 2007; 7:976-91.
4.
Marina O, Brusic V, WU CJ. Target discovery using proteomic microarrays. BIOforum Europe
2007; 11: 20-2.
5.
WU CJ. Allogeneic stem cell transplantation for the treatment of hemoglobinopathies. In: Soiffer,
RJ, editor. Stem Cell Transplantation for Hematologic Malignancies. New York: Springer-Verlag,
LLC; 2008. p. 201-21.
6.
WU CJ, Ritz J. Revealing tumor-specific immunity following allogeneic hematopoietic stem cell
transplantation. Clin Can Res 2009; 15: 4515-7.
7.
Marina O, Duke-Cohan JS, WU CJ. A co-precipitation-based validation methodology for
interactions identified using protein microarrays. Methods in Mol Biol 2011; 723: 239-54.
8.
Deluca DS, Marina O, Ray S, Zhang GL, WU CJ, Brusic V. Data processing and analysis for
protein microarrays. Methods in Mol Biol, 2011; 723:337-47.
26
9.
Hsieh MM, WU CJ, Tisdale JF. In mixed hematopoietic chimerism, the donor red cells win.
Haematologica 2011; 96: 1-3.
10. Brusic A, WU CJ. Anti-cancer vaccines following hematopoietic stem cell transplantation to
enhance graft-versus-leukemia responses. Front Biosci 2012; 17:635-55.
11. Chapman M, Warren EH 3rd, WU CJ. Applications of next-generation sequencing to blood and
marrow transplantation. Biol Blood Marrow Transplant 2012 18: S151-60.\
12. WU CJ. CLL clonal heterogeneity: an ecology of competing subpopulations. Blood 2012 Nov
15;120(20):4117-8. PMC Journal - In Process
13. Wan YZ, WU CJ. SF3B1 mutations in chronic lymphocytic leukemia. Blood. 2013 Apr 8. [Epub
ahead of print]
14. Landau DA WU CJ. Chronic lymphocytic leukemia at the forefront of high throughput genomic
investigation. Genome Med (in press)
15. Hacohen N, Fritsch EF, Carter TA, Lander ES, WU CJ. Getting personal with neoantigens-based
therapeutic vaccines. Cancer Immunology Research (in press).
•
Books/Textbooks for the medical or scientific community
1. WU CJ, editor. Protein Microarrays for Disease Analysis. New York: Humana Press: 2011.
Abstracts, Poster Presentations and Exhibits Presented at Professional Meetings
1.
Hainz U, Pozdnyakova O, Aldridge J, Kim HS, Canning CM, Soiffer RJ, Ritz J, Alyea EP,
WU CJ. Effective graft-versus-leukemia responses to donor lymphocyte infusion are
associated with pre-existing CD8+ T cell marrow infiltrates. American Society for Blood
and Marrow Transplantation; 2010 Feb 24-28; Orlando FL.
2.
Hainz U, Sievers QL, Stevenson KE, Goldstein NR, Dorfman DM, Brown JR, Freeman
GJ, WU CJ. Marrow-infiltrating T cells in patients with chronic lymphocytic leukemia
display functional impairment and express PD-1. American Society of Hematology; 2010
Orlando FL.
Narrative Report
Overall summary
Almost all of my major activities are devoted to basic science research; the rest to
27
teaching/mentoring and clinical duties. My research focuses on dissecting the underlying
mechanisms of pathobiology of chronic lymphocytic leukemia (CLL) as a means to more
rationally generate effective immune-based therapy for the treatment of this common adult
leukemia. These studies have resulted in several pioneering publications and many ongoing
projects. My teaching/mentoring includes: lectures on cancer vaccines, CLL genome analysis,
and post-transplant immune reconstitution; and mentoring of 4 medical students and 9
postdoctoral fellows. Clinical responsibilities include: 1 month attending per year on the BWH
blood/marrow transplantation service; and PI of a phase I/II study that I initiated of posttransplant whole tumor cell vaccination for CLL.
Area of Excellence: Investigation
(a) Understanding graft-versus-leukemia (GvL). I am investigating the basis for curative
responses following allogeneic stem cell transplantation, identifying components required for
effective anti-leukemia immunity in human CLL and chronic myeloid leukemia (CML). My
published studies have demonstrated that long-lived GvL responses are associated with
coordinated adaptive and innate polyclonal immune responses directed against antigens, such as
CML66 and CML28, that are highly expressed in leukemia progenitor cells but low in normal
tissue. We are now completing an analysis of the activation state of leukemia-infiltrating T cells
before and after allotransplantation for CML and CLL, which appear to be predictive of clinical
response.
(b) Whole tumor vaccines to augment the GvL effect. I am leading a high-priority clinical trial at
DFCI to examine the safety and immunologic effects of vaccination with whole tumor cells
(using irradiated autologous leukemia cells) and the cytokine adjuvant GM-CSF in posttransplant patients. Vaccinated subjects have developed CD8+ T cell responses to CLL-specific
antigens, independent of allo-immunity, implying that personalized whole tumor cell vaccination
can enhance anti-tumor immunity with minimal toxicity. Our completed and ongoing studies of
this vaccine are laying the groundwork for using the post-transplant setting as a platform for
developing tumor vaccines.
(c) Genome analysis of CLL. We integrated sequencing data of 91 CLL samples with clinical
annotation, defining 9 key mutated genes and 6 pathways involved in CLL pathogenesis, and
have discovered novel associations with prognostic factors. Our ongoing studies focus on: (1)
systematic analyses to couple tumor genotype with phenotype; (2) understanding CLL tumor
heterogeneity; (3) mechanistic studies of specific tumors drivers, such as SF3B1.
(d) Discovery of personalized tumor neoantigens. A high priority in cancer immunotherapy is
the identification of tumor-specific antigens that would allow effective tumor targeting without
collateral toxicity. We are pioneering the use of exome and transcriptome sequencing
technologies to identify unique mutated CLL antigens that arise from individual-specific genetic
alterations within a tumor, thus paving the way for developing personalized tumor vaccines.
Integration. As a physician-scientist, my goal is to move from bench to bedside and back to
patients to understand CLL biology and tumor vaccines, and to develop new treatments. My
studies have broad implications for understanding mechanisms of human tumor immunity and
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biology, dissecting existing methods of immunotherapy and devising new approaches to tumor
vaccines.
Significant Supporting Activity: Clinical Expertise
Given the close apposition of my laboratory research interests and its impact on clinical care, I
attend on the inpatient transplant service at BWH one month a year, and evaluate and enroll
patients for my clinical trials in the Hematologic Malignancies outpatient clinic, with a particular
focus on patients with chronic lymphocytic leukemia.
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