Dr. Hollenhorst is a physician and scientist with expertise in non-malignant hematology, transfusion medicine, and chemical biology. Dr. Hollenhorst values the one-on-one relationships that she forms with her patients, and strives to deliver the highest quality of care for individuals with blood diseases. Her experience caring for patients drives her to ask scientific questions in the laboratory, where she aims to bring a chemical approach to the study of non-malignant blood disease.

Dr. Hollenhorst pursued combined MD and PhD training at Harvard University, where she received a PhD in Chemical Biology under the mentorship of Professor Christopher T Walsh. She subsequently completed a residency in Internal Medicine at Brigham and Women's Hospital, a fellowship in Transfusion Medicine at Harvard Medical School, and a fellowship in Hematology at Stanford.

Dr. Hollenhorst has a particular interest in the biology of platelets, which are cellular fragments that help the blood to maintain a healthy balance between excessive bleeding and excessive clotting. Working in the laboratory of Professor Carolyn Bertozzi of Stanford Chemistry, Dr. Hollenhorst is studying sugar-containing molecules that are found within platelets and are important in controlling their function and lifespan.

Dr. Hollenhorst's research is supported by a Stanford Chemistry, Engineering & Medicine for Human Health Physician-Scientist Fellowship, a National Institutes of Health Individual Postdoctoral Fellowship, and a National Blood Foundation Early-Career Scientific Research Grant.

Clinical Focus

  • Non-malignant hematology
  • Transfusion medicine
  • Hemostasis and thrombosis
  • Sickle Cell Disease
  • Hematology

Academic Appointments

  • Clinical Instructor, Pathology

Honors & Awards

  • Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship (F32), National Institutes of Health, National Heart Lung Blood Institute (2019-2022)
  • Early-Career Scientific Research Grant, National Blood Foundation (2019-2021)
  • Physician-Scientist Research Fellowship, Stanford ChEM-H (2017-2020)
  • Certificate of Distinction in Teaching (Course: Chemistry 27, Organic Chemistry of Life), Harvard University (2010)
  • Award for Exemplary Leadership in Coordinating the MD/PhD-LHB Grand Rounds, Harvard-MIT MD/PhD Program (2010)
  • Fox Award for the Most Outstanding Undergraduate in the Department of Biological Sciences, Stanford University (2005)

Professional Education

  • Board Certification: Blood Banking/Transfusion Medicine, American Board of Pathology (2017)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2016)
  • Hematology Fellowship, Stanford (2019)
  • Transfusion Medicine Fellowship, Harvard Medical School (2017)
  • Internal Medicine Residency, Brigham and Women's Hospital (2016)
  • MD, Harvard Medical School (Harvard-MIT Health Sciences and Technology) (2013)
  • PhD, Harvard University, Chemical Biology (2011)


Graduate and Fellowship Programs

  • Hematology (Fellowship Program)
  • Transfusion Medicine (Fellowship Program)


All Publications

  • Thrombosis, Hypercoagulable States, and Anticoagulants PRIMARY CARE Hollenhorst, M. A., Battinelli, E. M. 2016; 43 (4): 619-+


    Patients with derangements of secondary hemostasis resulting from inherited or acquired thrombophilias are at increased risk of venous thromboemboli (VTE). Evaluation of a patient with suspected VTE proceeds via evidence-based algorithms that involve computing a pretest probability based on the history and physical examination; this guides subsequent work-up, which can include D dimer and/or imaging. Testing for hypercoagulable disorders should be pursued only in patients with VTE with an increased risk for an underlying thrombophilia. Direct oral anticoagulants are first-line VTE therapies, but they should be avoided in patients who are pregnant, have active cancer, antiphospholipid antibody syndrome, severe renal insufficiency, or prosthetic heart valves.

    View details for DOI 10.1016/j.pop.2016.07.001

    View details for Web of Science ID 000389510000009

    View details for PubMedID 27866581

  • A Head-to-Head Comparison of Eneamide and Epoxyamide Inhibitors of Glucosamine-6-Phosphate Synthase from the Dapdiamide Biosynthetic Pathway BIOCHEMISTRY Hollenhorst, M. A., Ntai, I., Badet, B., Kelleher, N. L., Walsh, C. T. 2011; 50 (19): 3859–61


    The dapdiamides make up a family of antibiotics that have been presumed to be cleaved in the target cell to enzyme-inhibitory N-acyl-2,3-diaminopropionate (DAP) warheads containing two alternative electrophilic moieties. Our prior biosynthetic studies revealed that an eneamide warhead is made first and converted to an epoxyamide via a three-enzyme branch pathway. Here we provide a rationale for this logic. We report that the R,R-epoxyamide warhead is a more efficient covalent inactivator of glucosamine-6-phosphate synthase by 1 order of magnitude versus the eneamide, and this difference correlates with a >10-fold difference in antibiotic activity for the corresponding acyl-DAP dipeptides.

    View details for PubMedID 21520904

  • The Nonribosomal Peptide Synthetase Enzyme DdaD Tethers N-beta-Fumaramoyl-L-2,3-diaminopropionate for Fe(II)/alpha-Ketoglutarate-Dependent Epoxidation by DdaC during Dapdiamide Antibiotic Biosynthesis (vol 132, pg 15773, 2010) JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Hollenhorst, M. A., Bumpus, S. B., Matthews, M. L., Bollinger, J., Kelleher, N. L., Walsh, C. T. 2011; 133 (5): 1609

    View details for DOI 10.1021/ja1110128

    View details for Web of Science ID 000287228500077

  • The ATP-Dependent Amide Ligases DdaG and DdaF Assemble the Fumaramoyl-Dipeptide Scaffold of the Dapdiamide Antibiotics BIOCHEMISTRY Hollenhorst, M. A., Clardy, J., Walsh, C. T. 2009; 48 (43): 10467–72


    The enzymes DdaG and DdaF, encoded in the Pantoea agglomerans dapdiamide antibiotic biosynthetic gene cluster, when expressed in Escherichia coli, form the tandem amide bonds of the dapdiamide scaffold at the expense of ATP cleavage. DdaG uses fumarate, 2,3-diaminopropionate (DAP), and ATP to make fumaroyl-AMP transiently on the way to the N(beta)-fumaroyl-DAP regioisomer. Then DdaF acts as a second ATP-dependent amide ligase, but this enzyme cleaves ATP to ADP and P(i) during amide bond formation. However, DdaF will not accept N(beta)-fumaroyl-DAP; the enzyme requires the fumaroyl moiety to be first converted to the fumaramoyl half-amide in N(beta)-fumaramoyl-DAP. DdaF adds Val, Ile, or Leu to the carboxylate of fumaramoyl-DAP to make dapdiamide A, B, or C, respectively. Thus, to build the dapdiamide antibiotic scaffold, amidation must occur on the fumaroyl-DAP scaffold, after DdaG action but before DdaF catalysis. This is an unusual instance of two ligases acting sequentially in untemplated amide bond formations using attack of substrate carboxylates at P(alpha) (AMP-forming) and then at P(gamma) (ADP-forming) of ATP cosubstrates.

    View details for PubMedID 19807062

  • Localized expression of an anti-TNF single-chain antibody prevents development of collagen-induced arthritis GENE THERAPY Smith, R., Tarner, I. H., Hollenhorst, M., Lin, C., Levicnik, A. U., Fathman, C. G., Nolan, G. P. 2003; 10 (15): 1248-1257


    Although systemic administration of neutralizing anti-TNF antibodies has been used successfully in treating rheumatoid arthritis, there is a potential for side effects. We transduced a collagen reactive T-cell hybridoma with tissue-specific homing properties to assess therapeutic effects of local delivery to inflamed joints of anti-TNF single-chain antibodies (scFv) by adoptive cellular gene therapy. Cell culture medium conditioned with 1 x 10(6) scFv producer cells/ml had TNF neutralizing capacity in vitro equivalent to 50 ng/ml anti-TNF monoclonal antibody. Adding a kappa chain constant domain to the basic scFv (construct TN3-Ckappa) gave increased in vitro stability and in vivo therapeutic effect. TN3-Ckappa blocked development of collagen-induced arthritis in DBA/1LacJ mice for >60 days. Transgene expression was detected in the paws but not the spleen of treated animals for up to 55 days postinjection. No significant variations in cell proliferation or cytokine secretion were found in splenocytes or peripheral lymphocytes. IL-6 expression was blocked in the diseased paws of mice in the scFv treatment groups compared to controls. In conclusion, we have shown that local expression of an anti-inflammatory agent blocks disease development without causing demonstrable systemic immune function changes. This is encouraging for the potential development of safe adoptive cellular therapies to treat autoimmunity.

    View details for DOI 10.1038/

    View details for Web of Science ID 000184207000007

    View details for PubMedID 12858190

  • GRAIL: An E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4(+) T cells IMMUNITY Anandasabapathy, N., Ford, G. S., Bloom, D., Holness, C., Paragas, V., Seroogy, C., Skrenta, H., Hollenhorst, M., Fathman, C. G., Soares, L. 2003; 18 (4): 535-547


    T cell anergy may serve to limit autoreactive T cell responses. We examined early changes in gene expression after antigen-TCR signaling in the presence (activation) or absence (anergy) of B7 costimulation. Induced expression of GRAIL (gene related to anergy in lymphocytes) was observed in anergic CD4(+) T cells. GRAIL is a type I transmembrane protein that localizes to the endocytic pathway and bears homology to RING zinc-finger proteins. Ubiquitination studies in vitro support GRAIL function as an E3 ubiquitin ligase. Expression of GRAIL in retrovirally transduced T cell hybridomas dramatically limits activation-induced IL-2 and IL-4 production. Additional studies suggest that GRAIL E3 ubiquitin ligase activity and intact endocytic trafficking are critical for cytokine transcriptional regulation. Expression of GRAIL after an anergizing stimulus may result in ubiquitin-mediated regulation of proteins essential for mitogenic cytokine expression, thus positioning GRAIL as a key player in the induction of the anergic phenotype.

    View details for Web of Science ID 000182353900009

    View details for PubMedID 12705856