NAME: Widemann, Brigitte C.

eRA COMMONS USER NAME (credential, e.g., agency login): WIDEMANNB

POSITION TITLE: Chief, Pediatric Oncology Branch, Center for Cancer Research, NCI;  Senior Investigator, Head Pharmacology & Experimental Therapeutics Section, Pediatric Oncology Branch (POB); Chief, POB

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

A. Personal Statement: 

As Chief of NCI’s Pediatric Oncology Branch, I am leading a group of diverse basic, translational and clinical researchers with the joint vision to improve the survival and quality of life of children and young adults with refractory or high-risk malignancies. I am leading a clinical trials program of new agents for the treatment of refractory childhood and adult solid tumors and genetic tumor predisposition syndromes (GTPS), in particular neurofibromatosis type 1 (NF1) related plexiform neurofibromas and malignant peripheral nerve sheath tumors. My team characterized the natural history of NF1 related tumors and identified the MEK inhibitor selumetinib as the first agent to shrink the majority of NF1 related plexiform neurofibromas and to provide clinical benefit. Based on the results of our clinical trials, selumetinib was approved by the FDA and in many countries for children with NF1 and symptomatic inoperable plexiform neurofibromas. In addition to therapeutic trials, I am leading an observational study for people with NF1 at increased risk for development of malignant peripheral nerve sheath tumors, which includes longitudinal monitoring with whole body MRI, liquid biomarkers and tissue samples. I also have a focus is on rare tumors. I am working with the NCI Childhood Cancer Data Initiative (CCDI) on the development of a CCDI led national pediatric, adolescent and young adult (AYA) rare cancer initiative.

B. Positions and Honors

Positions and Employment

2022-present             Special Advisor to the NCI Director for Childhood Cancer

2019-2020                 Acting Chief, Immune Deficiency and Cellular Therapy Program, NCI

2016-2021           NCI, Center for Cancer Research, Deputy Director

2017-present             Chief, NCI Pediatric Oncology Branch

2009-present             Head, Pharmacology and Experimental Therapeutics Section, POB, NCI

2009-present             Senior Investigator, Pediatric Oncology Branch, National Cancer Institute, NIH

2000-2009                 Tenure-Track Investigator, Pediatric Oncology Branch, National Cancer Institute, NIH

1992-1995                 Fellow, Pediatric Oncology Branch, National Cancer Institute, NIH

1995-1999                 Clinical Associate, Pediatric Oncology Branch, National Cancer Institute, NIH

1986-1992                 Pediatric Residency, University Children’s Hospital Cologne, Cologne, Germany

Other Experience and Professional Memberships

2024-present   Chair, Children’s Cancer Foundation Scientific Advisory Board

2023-present   Co-Director, NCI Cancer Prevention Clinic                        

2023-present    US Co-Chair: Technical working group on childhood and young adult cancer, EU Beating Cancer Plan-US NCI Cancer Moonshot Collaboration

2023-present    Co-chair, Memorial Sloan Kettering Cancer Center Pediatric Data Safety Monitoring Committee

2022-2022       Federal Chief Medical Officer Deployment to Fort Bliss for Unaccompanied Children Program, El Paso, TX

2022-present   Member SARC Discovery Translation Committee

2021-2023       Co-Chair, NCI Childhood Cancer Data Initiative (CCDI) Engagement Committee

2022-present   Co-Chair: Pediatric Strategic Planning at the NIH Clinical Center Committee

2022-present   Member, NCI Childhood Cancer Data Initiative (CCDI) Strategic Leadership Team

2019-2020.   Member the National Academies of Sciences, Engineering and Medicine: Committee on  Childhood Cancers and Disability.

2019-present    Co-Chair, AstraZeneca Pediatric Oncology External Steering Committee

2018-present    Member, NIH Pediatric Research Consortium (N-PeRC)

2018-present    Co-founder and advisor, Advancing RAS/RASopathy Therapies (ART)  

2018-present    Member, Clinical Investigator Review Panel advisory to NIH Central Tenure  Committee  

2000-present    Member, American Society of Clinical Oncology

1994-present    Member American Association for Cancer Research since 1994

1994-present    Member Children’s Oncology Group

2021-present    Member Association of American Physicians 2021

2019-present    Co-Chair, AstraZeneca Pediatric Oncology External Steering Committee

2019-present    Member, Medical Advisory Committee, Children’s Tumor Foundation

2016-present    Member, Scientific Advisory Board, Children’s Cancer Foundation

2016-present    Member, Pediatric and Adolescent Solid Tumor Steering Committee (PASTSC), NCI

2012-present    Member, Scientific advisory board Neurofibromatosis Therapeutic Acceleration Program

2011-present    Member (previously chair, co-chair), MPNST Committee of DoD Sponsored NF Consortium

2011-present    Member (previously chair), Plexiform Neurofibroma Committee of DoD NFCTC

2010-2021        NCI PI for Children’s Oncology Group Pediatric Early Phase Clinical Trials Network

2017-2018        Chair, Clinical Investigator Development Program, NCI, Center for Cancer Research

2006-present    NCI PI for DoD Sponsored NF Consortium

2014-2018        Member, CCR Science Board

2008-2016        NCI Women Scientist Advisor

2006-2010        Chair, NCI Safety Monitoring Committee

2001-2008        Member NCI Scientific Protocol Review and Monitoring Committee

1997-present    Member, POB Protocol Review Committee

Honors

2024  HHS Departmental Award for Meritorious Service (the second highest honor award granted)

2023  NCI Director’s group award for establishment of the Cancer Prevention Clinic at the NIH

2022  NIH Women Scientist Advisors: Anita Roberts Lecture: Advancing the Development of Effective Therapies for Children and Adults with Rare Tumors

2021 Clinical Research Forum: Top 10 and Distinguished Clinical Research Achievement Award for    “Selumetinib in Children with Inoperable Plexiform Neurofibromas

2021   24th Astute Clinician NIH Wednesday Afternoon Lecture (WALS)

2021   Samuel J. Heyman Service to America Medals Finalist

2021   Member of the Association of American Physicians

2021   AACR-Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research

2019   NIH Director Award as member for innovative work creating novel clinical research opportunities at the NCI and   NIH to develop therapies for patients with unmet clinical needs

2018  NCI Director’s Award for outstanding scientific contributions to the understanding and development of effective therapies for rare tumors

2018   NCI Women Scientist Advisors Mentoring and Leadership Award

2017  NCI Director’s Group Award for establishing the Rare Tumors Initiative in the CCR and advancing collaboration and research in the field of rare tumors

2016  Children’s Tumor Foundation Humanitarian Award

2013  Friedrich von Recklinghausen Award from the Children’s Tumor Foundation

2009  NCI Director’s Award for development of NF1 program

2008  NIH merit award to carboxypeptidase transition group

2006  NIH Director’s Award for developing clinical research program for NF1 related tumors

2003  Make a Difference Award, Neurofibromatosis, Inc.-Mid-Atlantic

1999  American Society of Clinical Oncology Merit Award

1997  Liese-Meitner Scholarship for Women in Science

1988  Doctor Medicinae “Magna Cum Laude”, Cologne, Germany

1986  North-Rhine-Westphalia State Scholarship for completion of doctoral thesis

3. Contribution to Science

1. I had a leadership role in the preclinical and clinical development of glucarpidase (carboxypeptidase-G₂), a highly effective, non-toxic, lifesaving antidote for the approximately 2% of patients who develop renal dysfunction following high-dose methotrexate (MTX) therapy, or for the rare patient who receives an accidental intrathecal MTX overdose. Glucarpidase is a bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites. Our clinical and pharmacokinetic analyses confirmed that early intervention with standard rescue approaches and glucarpidase are highly effective in patients who develop high-dose MTX-induced renal dysfunction. Glucarpidase was approved by the FDA for MTX induced renal dysfunction in January 2012.

1. Widemann BC, Hetherington ML, Murphy RF, Balis FM, Adamson PC: Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity. Cancer 76:521-6, 1995. PMID: 8625136.
2. Widemann BC, Balis FM, Murphy RF, Sorensen JM, Montello MJ, O'Brien M, Adamson PC: Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. J Clin Oncol 15:2125-34, 1997. PMID: 9164227.
3. Widemann BC, Balis FM, Shalabi A, Boron M, O'Brien M, Cole DE, Jayaprakash N, Ivy P, Castle V, Muraszko K, Moertel CL, Trueworthy R, Hermann RC, Moussa A, Hinton S, Reaman G, Poplack D, Adamson PC: Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2. J Natl Cancer Inst 96:1557-9, 2004. PMID: 15494606
4. Widemann BC, Balis FM, Kim A, Boron M, Jayaprakash N, Shalabi A, O'Brien M, Eby M, Cole DE, Murphy RF, Fox E, Ivy P, Adamson PC: Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol 28:3979-86, 2010 PMCID: PMC6642810.

2. I direct a comprehensive clinical trials program for NF1 related plexiform neurofibromas (PN). I developed novel trial designs and endpoints, which allow for meaningful conduct of clinical trials in NF1. We pioneered the use of volumetric MRI analysis of PN in clinical trials, which is now uniformly accepted. I have directed multiple clinical trials directed at NF1 PN and collaborate with preclinical and clinical investigators, cooperative groups, and consortia in the clinical translation of findings. We identified the MEK inhibitor selumetinib as the first agent with substantial activity in children with NF1 and PN. Based on clinical trials I directed, selumetinib was the first medical therapy to be approved by the FDA and EMA for children with NF1 PN. We recently identified that selumetinib also shrinks PN in adults and provides clinical benefit. Jointly with Dr. Scott Plotkin, I am co-chairing the international working group: Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS).

1. 1. Dombi E, Ardern-Holmes SL, Babovic-Vuksanovic D, Barker FG, Connor S, Evans DG, Fisher MJ, Goutagny S, Harris GJ, Jaramillo D, Karajannis MA, Korf BR, Mautner V, Plotkin SR, Poussaint TY, Robertson K, Shih CS, Widemann BC, Collaboration REiNS: Recommendations for imaging tumor response in neurofibromatosis clinical trials. Neurology 81:S33-40, 2013 PMCID: PMC6642810.
   2. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC: Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. N Engl J Med 375:2550-2560, 2016 PMCID: PMC6642810.
   3. Gross AM, Wolters PL, Dombi E, Baldwin A, Whitcomb P, Fisher MJ, Weiss B, Kim A, Bornhorst M, Shah AC, Martin S, Roderick MC, Pichard DC, Carbonell A, Paul SM, Therrien J, Kapustina O, Heisey K, Clapp DW, Zhang C, Peer CJ, Figg WD, Smith M, Glod J, Blakeley JO, Steinberg SM, Venzon DJ, Doyle LA, Widemann BC: Selumetinib in Children with Inoperable Plexiform Neurofibromas. N Engl J Med 382:1430-1442, 2020 PMCID: PMC7305659.
   4. Gross AM, O'Sullivan Coyne G, Dombi E, Tibery C, Herrick WG, Martin S, Angus SP, Shern JF, Rhodes SD, Foster JC, Rubinstein LV, Baldwin A, Davis C, Dixon SAH, Fagan M, Ong MJ, Wolters PL, Tamula MA, Reid O, Sankaran H, Fang F, Govindharajulu JP, Browne AT, Kaplan RN, Heisey K, On TJ, Xuei X, Zhang X, Johnson BC, Parchment RE, Clapp DW, Srivastava AK, Doroshow JH, Chen AP, Widemann BC: Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial. Nat Med 31:105-115, 2025.(Submitted to Pubmed Central)

3. I coordinate a clinical trials program studying the malignant transformation of histologically benign peripheral nerve sheath tumors in NF1 to atypical neurofibromas and highly aggressive malignant peripheral nerve sheath tumors (MPNST). I am directing interventional trials for MPNST and a surveillance study for people with NF1 at increased risk of MPNST. We have characterized the clinical presentation of atypical neurofibromas as precursor lesions for NF1 MPNST and have developed strategies to prevent MPNST.

1. Higham CS, Dombi E, Rogiers A, Bhaumik S, Pans S, Connor SEJ, Miettinen M, Sciot R, Tirabosco R, Brems H, Baldwin A, Legius E, Widemann BC, Ferner RE. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheathtumors. Neuro Oncol 2018;20:818-25 PMCID: PMC6642810.
2. Reilly KM, Kim A, Blakely J, Ferner RE, Gutmann DH, Legius E, Miettinen MM, Randall RL, Ratner N, Jumbe NL, Bakker A, Viskochil D, Widemann BC, Stewart DR: Neurofibromatosis Type 1-Associated MPNST State of the Science: Outlining a Research Agenda for the Future. J Natl Cancer Inst 109, 2017 PMCID: PMC6642810.
3. Akshintala S, Baldwin A, Liewehr DJ, Goodwin A, Blakeley JO, Gross AM, Steinberg SM, Dombi E, Widemann BC: Longitudinal evaluation of peripheral nerve sheath tumors in neurofibromatosis type 1: Growth analysis of plexiform neurofibromas and distinct nodular lesions. Neuro Oncol, 2020. PMCID: PMC7523449.
4. Kim A, Lu Y, Okuno SH, Reinke D, Maertens O, Perentesis J, Basu M, Wolters PL, De Raedt T, Chawla S, Chugh R, Van Tine BA, O'Sullivan G, Chen A, Cichowski K, Widemann BC: Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023). Sarcoma 2020:5784876, 2020 PMCID: PMC7305659.

4. I have developed and coordinate a clinical trials program for children and young adults with rare solid tumors or GTPS. I am studying the natural history of these tumors and develop targeted therapies. With support of Cancer Moonshot funding I am co-leading a collaboration to establish a rare tumor patient engagement network called My Pediatric and Adolescent Rare Tumor  (MyPART) Network. I co-developed a comprehensive natural history of rare solid tumor trial at the NIH. In addition, we engage advocates, patients and intramural and extramural researchers. As a member of NCI’s Childhood Cancer Data Initiative (CCDI) I am contributing to efforts developing a national program for children and young adults with very rare tumors.

1. Wedekind MF, Reilly KM, Rivero JD, Lockridge R, Allen T, Raygada M, Bernstein D, Thomas BJ, Vivelo C, Levine J, Shonkoev N, Aldape K, Glod J, Sandler AB, Widemann BC. NCI intramural program approach to rare tumors: Natural history study of rare solid tumors in children and adults: A longitudinal, comprehensive data and biospecimen collection protocol. Pediatr Blood Cancer, epub ahead of print, 2023 PMCID: PMC10733551
2. Gross AM, Frone M, Gripp KW, Gelb BD, Schoyer L, Schill L, Stronach B, Biesecker LG, Esposito D, Hernandez ER, Legius E, Loh ML, Martin S, Morrison DK, Rauen KA, Wolters PL, Zand D, McCormick F, Savage SA, Stewart DR, Widemann BC, Yohe ME: Advancing RAS/RASopathy therapies: An NCI-sponsored intramural and extramural collaboration for the study of RASopathies. Am J Med Genet A 182:866-876, 2020 PMCID: PMC7456498
3. Subashini J, Mardis ER, Wedekind MF, Widemann BC, Kingery RK, Gonzalez SL, Shern JF, Reaman GH. Childhood cancer data initiative: Status report. Pediatr Blood Cancer, epub ahead of print, 2023. PMCID: PMC12360469
4. Kraft IL, Akshintala S, Zhu Y, Lei H, Derse-Anthony C, Dombi E, Steinberg SM, Lodish M, Waguespack SG, Kapustina O, Fox E, Balis FM, Merino MJ, Meltzer PS, Glod JW, Shern JF, Widemann BC: Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib. Clin Cancer Res 24:753-765, 2018 PMCID: PMC6642810.

Complete list of Published Work in MyBibliography:

 https://www.ncbi.nlm.nih.gov/myncbi/brigitte.widemann.1/bibliography/public/