Stefan  Ambs, Ph.D., M.P.H.

Stefan Ambs, Ph.D., M.P.H.

  • Center for Cancer Research
  • National Cancer Institute


Dr. Ambs conducts integrative epidemiology studies of prostate cancer and breast cancer and utilizes epidemiological and translational research to identify risk factors and pathways that influence tumor development and progression. His research includes genome-wide analysis of gene expression and evaluation of the tumor metabolome, cancer health disparity, discovery of prognostic and predictive disease biomarkers, smoking and prostate cancer metastasis, and the analysis of genetic variations and their association with cancer using candidate gene approaches and genome-wide applications. This research led to the discovery of an immune signature in tumors of African-American patients and established aberrant expression of inducible nitric oxide synthase as a predictor of poor survival in breast cancer.

Areas of Expertise

Molecular Epidemiology
Cancer Risk Assessment 
Nitric Oxide (NO)


Selected Key Publications

MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis

Terunuma A, Putluri N, Mishra P, Mathé EA, Dorsey TH, Yi M, Wallace TA, Issaq HJ, Zhou M, Killian JK, Stevenson HS, Karoly ED, Chan K, Samanta S, Prieto D, Hsu TY, Kurley SJ, Putluri V, Sonavane R, Edelman DC, Wulff J, Starks AM, Yang Y, Kittles RA, Yfantis HG, Lee DH, Ioffe OB, Schiff R, Stephens RM, Meltzer PS, Veenstra TD, Westbrook TF, Sreekumar A, Ambs S.
J. Clin. Invest. 124: 398-412, 2014. [ Journal Article ]

Liver- and Microbiome-derived Bile Acids Accumulate in Human Breast Tumors and Inhibit Growth and Improve Patient Survival.

Tang W, Putluri V, Ambati CR, Dorsey TH, Putluri N, Ambs S.
Clin Cancer Res. 25(19): 5972-83, 2019. [ Journal Article ]

Urinary Thromboxane B2 and Lethal Prostate Cancer in African American Men.

Kiely M, Milne GL, Minas TZ, Dorsey TH, Tang W, Smith CJ, Baker F, Loffredo CA, Yates C, Cook MB, Ambs S
J Natl Cancer Institute. djab129: 2021. [ Journal Article ]

Integrated proteotranscriptomics of breast cancer reveals globally increased protein-mRNA concordance associated with subtypes and survival.

Tang W, Zhou M, Dorsey TH, Prieto DA, Wang XW, Ruppin E, Veenstra TD, Ambs S.
Genome Med. 10(1): 94, 2018. [ Journal Article ]

IFNL4-ΔG Allele Is Associated with an Interferon Signature in Tumors and Survival of African-American Men with Prostate Cancer.

Tang W, Wallace TA, Yi M, Magi-Galluzzi C, Dorsey TH, Onabajo OO, Obajemu A, Jordan SV, Loffredo CA, Stephens RM, Silverman RH, Stark GR, Klein EA, Prokunina-Olsson L, Ambs S.
Clin Cancer Res. 24(21): 5471-81, 2018. [ Journal Article ]

Job Vacancies

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Postbaccalaureate Fellow (CRTA) - NIMHD
Anuoluwapo Ajao, B.S.
Postdoctoral Fellow (Cancer Prevention Fellow)
Maeve L. Bailey-Whyte , Ph.D., M.P.H.
Research Biologist/Laboratory Manager
Tiffany Howe Dorsey, B.S.
Postdoctoral Fellow (Cancer Prevention Fellow)
Brittany Lord, Ph.D., M.P.H.
Postdoctoral Fellow (Visiting)
Tsion Minas, Ph.D.
Research Fellow
Gatikrushna Panigrahi, Ph.D.
Special Volunteer
Margaret Pichardo, Ph.D., M.S.
Special Volunteer
Wei Tang, Ph.D.
Postbaccalaureate Fellow (CRTA)
Amy Luo Zhang, B.S.


Cover of The Journal of Clinical Investigation, January 2, 2018

ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming

Published Date

The cover image depicts the role of mitochondrial ADHFE1 in D-2-hydroxyglutarate production, highlighting the contributions of the enzyme and oncometabolite to breast cancer progression.

Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG–producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival. We found that MYC upregulates ADHFE1 through changes in iron metabolism while coexpression of both ADHFE1 and MYC strongly enhanced orthotopic tumor growth in MCF7 cells. Moreover, ADHFE1 promoted metabolic reprogramming with increased formation of D-2HG and reactive oxygen, a reductive glutamine metabolism, and modifications of the epigenetic landscape, leading to cellular dedifferentiation, enhanced mesenchymal transition, and phenocopying alterations that occur with high D-2HG levels in cancer cells with IDH mutations. Together, our data support the hypothesis that ADHFE1 and MYC signaling contribute to D-2HG accumulation in breast tumors and show that D-2HG is an oncogenic metabolite and potential driver of disease progression.


ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming. Mishra P, Tang W, Putluri V, Dorsey TH, Jin F, Wang F, Zhu D, Amable L, Deng T, Zhang S, Killian JK, Wang Y, Minas TZ, Yfantis HG, Lee DH, Sreekumar A, Bustin M, Liu W, Putluri N, and Ambs S.  J Clin Invest. 128(1):323-340, 2018.