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Nicole Michmerhuizen, Ph.D.

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Call Center (585) 276-3000

About Me

Dr. Michmerhuizen earned her bachelor’s degree from Calvin University, studying chemical engineering and biochemistry. She then obtained her PhD in Pharmacology from the University of Michigan, where she completed her thesis in the lab of Dr. J. Chad Brenner studying combination therapies in head an...
Dr. Michmerhuizen earned her bachelor’s degree from Calvin University, studying chemical engineering and biochemistry. She then obtained her PhD in Pharmacology from the University of Michigan, where she completed her thesis in the lab of Dr. J. Chad Brenner studying combination therapies in head and neck squamous cell carcinoma. As a graduate student, Nicole also developed an interest in translational cancer research. She went on to complete her postdoctoral training at St. Jude Children’s Research Hospital in the lab of Dr. Charles Mullighan. Her postdoctoral studies focused on the biology and therapeutic targeting of NUP98 fusion oncoproteins, a hallmark of high-risk leukemia in children.

Faculty Appointments

Assistant Professor - Department of Pediatrics, Hematology and Oncology (SMD)

Research

NUP98 rearrangements are observed in several hematological malignancies, but occur most commonly in acute myeloid leukemia (AML) where they comprise 5% of pediatric and 3% of adult cases. NUP98 fusion oncoproteins are one of the most frequent genetic alterations in relapsed childhood AML and predict...
NUP98 rearrangements are observed in several hematological malignancies, but occur most commonly in acute myeloid leukemia (AML) where they comprise 5% of pediatric and 3% of adult cases. NUP98 fusion oncoproteins are one of the most frequent genetic alterations in relapsed childhood AML and predict poor prognoses. NUP98 fusion oncoproteins retain the N-terminal, intrinsically-disordered region of NUP98, as well as the C-terminal portion of one of over 30 fusion partners. Most partner genes include a DNA-binding or chromatin-modifying domain, which contributes to the ability of the fusion to interact with DNA and drive a stem cell-like gene expression program. Few effective therapies are available for NUP98-rearranged leukemia, and relapse occurs in nearly 70% of children with NUP98 fusion-expressing AML. These dire outcomes motivate studies to improve our mechanistic understanding of NUP98-rearranged leukemia with the goal of developing new strategies to improve patient survival.

Previous work from Dr. Michmerhuizen and others showed that NUP98 fusions localize in membrane-less organelles called condensates, which form through liquid-liquid phase separation (Ahn et al, Nature 2021; Chandra, Michmerhuizen, Shirnekhi, Tripathi et al, Cancer Discovery 2022). These condensates have a critical role in leukemic cell transformation and gene deregulation. Dr. Michmerhuizen and co-authors further characterized NUP98 fusion-associated condensates and identified their protein composition, which revealed both known and novel fusion interactors. Among these interactors were members of MYST family histone acetyltransferase complexes, KAT6A/MOZ and KAT7/HBO1. Genetic or pharmacologic targeting of KAT6A/7 led to decreased cell fitness in multiple mouse and human models of NUP98-rearranged leukemia. Moreover, treating NUP98 fusion-bearing patient derived xenografts with KAT6A/7 inhibitor PF9363 led to myeloid differentiation, reduced leukemia burden, and synergism with Menin inhibition (Michmerhuizen et al, Cancer Discovery 2025). These findings nominate KAT6A/7 inhibition as a promising treatment strategy in NUP98-rearranged leukemia and motivate additional studies to investigate therapeutic targeting of other NUP98 FO interactors.

The current focus of the Michmerhuizen lab is to understand the composition of fusion oncoprotein-associated condensates and therapeutic vulnerabilities. This work will provide new opportunities to undermine the biology of NUP98 and other fusion oncoproteins and in doing so develop more effective therapeutic strategies for fusion-driven cancers.

Publications

Journal Articles

KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia.

Michmerhuizen NL, Heikamp EB, Iacobucci I, Umeda M, Arthur B, Mishra V, Park CS, Di Giacomo D, Hiltenbrand R, Gao Q, Radko-Juettner S, Lott J, Martucci C, Subramanyam V, Hatton C, Wenge DV, Baviskar P, Portola P, Claquin A, Chandra B, Baggett DW, Khalighifar A, Huang H, Zhou P, Long L, Shi H, Sun Y, Papachristou EK, Sekhar Reddy Chilamakuri C, de Luna Vitorino FN, Gongora JM, Wu H, Pounds SB, Janke LJ, Kentsis A, D'Santos CS, Garcia BA, Kriwacki RW, Chi H, Klco JM, Armstrong SA, Mullighan CG

Cancer discovery.. 2025 October 615 (10):2096-2116. Epub 1900 01 01.

Fusion Oncoproteins and Cooperating Mutations Define Disease Phenotypes in NUP98-Rearranged Leukemia.

Umeda M, Hiltenbrand RL, Michmerhuizen NL, Barajas JM, Thomas ME, Arthur B, Walsh MP, Song G, Ma JJ, Westover T, Kumar A, Pölönen P, Mecucci C, Di Giacomo D, Locatelli F, Masetti R, Bertuccio SN, Pigazzi M, Pruett-Miller SM, Pounds SB, Rubnitz J, Inaba H, Papadopoulos KP, Wick MJ, Iacobucci I, Mullighan CG, Klco JM

Blood.. 2025 July 23 Epub 07/23/2025.

Long read sequencing identifies complex structural variant landscape and recurrent TERT rearrangements in mucoepidermoid carcinoma.

Gensterblum-Miller E, Bhangale A, Majid DA, Pienkowski VM, Rydzanicz M, Janiszewska J, Kostrzewska-Poczekaj M, Chang C, Brummel C, Michmerhuizen NL, Wang J, Sandford E, Tewari M, Wierzbicka M, Birkeland AC, McHugh JB, Spector ME, Giefing M, Jarmuz-Szymczak M, Heft Neal ME, Brenner JC

Oral oncology.. 2024 December 159 :107108. Epub 11/15/2024.

Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma.

Ludwig ML, Michmerhuizen NL, Wang J, Birkeland AC, Majchrowski BK, Nimmagadda S, Zhai J, Bhangale A, Kulkarni A, Jiang H, Swiecicki PL, Brenner JC

Archives of oral biology.. 2023 December 156 :105822. Epub 10/11/2023.

Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.

Michmerhuizen NL, Ludwig ML, Birkeland AC, Nimmagadda S, Zhai J, Wang J, Jewell BM, Genouw D, Remer L, Kim D, Foltin SK, Bhangale A, Kulkarni A, Bradford CR, Swiecicki PL, Carey TE, Jiang H, Brenner JC

Head & neck.. 2022 May 44 (5):1192-1205. Epub 02/27/2022.

Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation.

Chandra B, Michmerhuizen NL, Shirnekhi HK, Tripathi S, Pioso BJ, Baggett DW, Mitrea DM, Iacobucci I, White MR, Chen J, Park CG, Wu H, Pounds S, Medyukhina A, Khairy K, Gao Q, Qu C, Abdelhamed S, Gorman SD, Bawa S, Maslanka C, Kinger S, Dogra P, Ferrolino MC, Di Giacomo D, Mecucci C, Klco JM, Mullighan CG, Kriwacki RW

Cancer discovery.. 2022 April 112 (4):1152-1169. Epub 1900 01 01.

Combined Pik3ca-H1047R and loss-of-function Notch1 alleles decrease survival time in a 4-nitroquinoline N-oxide-driven head and neck squamous cell carcinoma model.

Michmerhuizen NL, Heenan C, Wang J, Leonard E, Bellile E, Loganathan SK, Wong SY, Lei YL, Brenner JC

Oral oncology.. 2022 March 126 :105770. Epub 02/13/2022.

Advancement of PI3 Kinase Inhibitor Combination Therapies for PI3K-Aberrant Chordoma.

Heft Neal ME, Michmerhuizen NL, Kovatch KJ, Owen JHJ, Zhai J, Jiang H, McKean EL, Prince MEP, Brenner JC

Journal of neurological surgery. Part B, Skull base.. 2022 February 83 (1):87-98. Epub 10/12/2020.

Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies.

Michmerhuizen NL, Klco JM, Mullighan CG

Blood.. 2020 November 12136 (20):2275-2289. Epub 1900 01 01.

Rationale for the advancement of PI3K pathway inhibitors for personalized chordoma therapy.

Michmerhuizen NL, Owen JH, Heft Neal ME, Mann JE, Leonard E, Wang J, Zhai J, Jiang H, McHugh JB, Brenner JC, Prince MEP

Journal of neuro-oncology.. 2020 March 147 (1):25-35. Epub 02/17/2020.

Head and Neck Cancer Immunotherapy beyond the Checkpoint Blockade.

Heath BR, Michmerhuizen NL, Donnelly CR, Sansanaphongpricha K, Sun D, Brenner JC, Lei YL

Journal of dental research.. 2019 September 98 (10):1073-1080. Epub 07/24/2019.

Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma.

Michmerhuizen NL, Leonard E, Matovina C, Harris M, Herbst G, Kulkarni A, Zhai J, Jiang H, Carey TE, Brenner JC

Molecular pharmacology.. 2019 May 95 (5):528-536. Epub 03/11/2019.

The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines.

Ludwig ML, Kulkarni A, Birkeland AC, Michmerhuizen NL, Foltin SK, Mann JE, Hoesli RC, Devenport SN, Jewell BM, Shuman AG, Spector ME, Carey TE, Jiang H, Brenner JC

Oral oncology.. 2018 December 87 :144-151. Epub 11/08/2018.

Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low-risk, nontraditional patients.

Gingerich MA, Smith JD, Michmerhuizen NL, Ludwig M, Devenport S, Matovina C, Brenner C, Chinn SB

Head & neck.. 2018 May 40 (5):943-954. Epub 02/10/2018.

Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma.

Hoesli R, Birkeland AC, Rosko AJ, Issa M, Chow KL, Michmerhuizen NL, Mann JE, Chinn SB, Shuman AG, Prince ME, Wolf GT, Bradford CR, McHugh JB, Brenner JC, Spector ME

Oral oncology.. 2018 February 77 :83-89. Epub 12/23/2017.

Genomic sequencing and precision medicine in head and neck cancers.

Hoesli RC, Ludwig ML, Michmerhuizen NL, Rosko AJ, Spector ME, Brenner JC, Birkeland AC

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.. 2017 May 43 (5):884-892. Epub 12/15/2016.

Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid carcinoma.

Birkeland AC, Foltin SK, Michmerhuizen NL, Hoesli RC, Rosko AJ, Byrd S, Yanik M, Nor JE, Bradford CR, Prince ME, Carey TE, McHugh JB, Spector ME, Brenner JC

Oral oncology.. 2017 May 68 :5-8. Epub 03/10/2017.

Surveilling the Potential for Precision Medicine-driven PD-1/PD-L1-targeted Therapy in HNSCC.

Mann JE, Hoesli R, Michmerhuizen NL, Devenport SN, Ludwig ML, Vandenberg TR, Matovina C, Jawad N, Mierzwa M, Shuman AG, Spector ME, Brenner JC

Journal of Cancer.. 2017 8 (3):332-344. Epub 02/09/2017.

Identification of Targetable ERBB2 Aberrations in Head and Neck Squamous Cell Carcinoma.

Birkeland AC, Yanik M, Tillman BN, Scott MV, Foltin SK, Mann JE, Michmerhuizen NL, Ludwig ML, Sandelski MM, Komarck CM, Carey TE, Prince ME, Bradford CR, McHugh JB, Spector ME, Brenner JC

JAMA otolaryngology-- head & neck surgery.. 2016 June 1142 (6):559-67. Epub 1900 01 01.

Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine.

Michmerhuizen NL, Birkeland AC, Bradford CR, Brenner JC

Genes & cancer.. 2016 May 7 (5-6):182-200. Epub 1900 01 01.

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity.

Pope WH, Bowman CA, Russell DA, Jacobs-Sera D, Asai DJ, Cresawn SG, Jacobs WR, Hendrix RW, Lawrence JG, Hatfull GF, , ,

eLife.. 2015 April 284 :e06416. Epub 04/28/2015.

Poly(amidoamine) dendrimer-methotrexate conjugates: the mechanism of interaction with folate binding protein.

van Dongen MA, Rattan R, Silpe J, Dougherty C, Michmerhuizen NL, Van Winkle M, Huang B, Choi SK, Sinniah K, Orr BG, Banaszak Holl MM

Molecular pharmaceutics.. 2014 November 311 (11):4049-58. Epub 10/01/2014.

An isothermal titration and differential scanning calorimetry study of the G-quadruplex DNA-insulin interaction.

Timmer CM, Michmerhuizen NL, Witte AB, Van Winkle M, Zhou D, Sinniah K

The journal of physical chemistry. B. 2014 February 20118 (7):1784-90. Epub 02/04/2014.

Cytotoxic and hemolytic effects of Tritrichomonas foetus on mammalian cells.

Burgess DE, Knoblock KF, Daugherty T, Robertson NP

Infection and immunity.. 1990 November 58 (11):3627-32. Epub 1900 01 01.