Experimental Hematology and Cancer Biology
Mulloy Lab

Mulloy Research Lab

Our research focuses on modeling leukemia using human hematopoietic stem and progenitor cells (HSPC). This allows us to establish relevant model systems to dissect the process of human myeloid and lymphoid leukemogenesis and to investigate the prevailing theory that acute myeloid leukemia is a stem cell disease.

We are focusing on three of the most common types of human leukemia: those associated with translocations between chromosomes 8 and 21, aberrations of chromosome 16, and translocations involving chromosome 11q23 that affect the MLL gene. Together, the subtypes of leukemia associated with these genetic lesions account for about 30 percent of all human acute leukemia cases.

Our studies of human leukemogenesis aim to answer a number of research questions. We want to understand the effects of AML1-ETO expression on the self-renewal and differentiation properties of human HSPC. We seek to identify the domains of AML1-ETO and the binding partners that are critical for function of the protein. We hope to develop relevant in vivo models of human leukemia using transplantation of these cells into immunocompromised mouse models, and intend to use these mouse models for therapeutic testing of novel compounds. Finally, we are investigating the role played by the Rac, Cdc42 and Rho proteins, members of the Rho family of small GTPases, in the development and maintenance of leukemia.

Publications

Wunderlich, M; Manning, N; Sexton, C; O’Brien, E; Byerly, L; Stillwell, C; Perentesis, JP; Mulloy, JC; Mizukawa, B. PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia. Frontiers in Oncology. 2021; 11:642466.

Su, R; Dong, L; Li, Y; Gao, M; Han, L; Wunderlich, M; Deng, X; Li, H; Huang, Y; Gao, L; et al. Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion. Cancer Cell. 2020; 38:79-96.e11.

Rodriguez, S; Abundis, C; Boccalatte, F; Mehrotra, P; Chiang, MY; Yui, MA; Wang, L; Zhang, H; Zollman, A; Bonfim-Silva, R; et al. Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL. Leukemia. 2020; 34:1241-1252.

Hinge, A; He, J; Bartram, J; Javier, J; Xu, J; Fjellman, E; Sesaki, H; Li, T; Yu, J; Wunderlich, M; et al. Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition. Cell Stem Cell. 2020; 26:420-430.e6.

Khodoun, MV; Morris, SC; Angerman, E; Potter, C; Schuman, R; Wunderlich, M; Maciag, JJ; Locker, KC S; Mulloy, JC; Herr, AB; et al. Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies. Journal of Allergy and Clinical Immunology. 2020; 145:907-921.e3.

Wunderlich, M; Manning, N; Sexton, C; Sabulski, A; Byerly, L; O'Brien, E; Perentesis, JP; Mizukawa, B; Mulloy, JC. Improved chemotherapy modeling with RAG-based immune deficient mice. Editor, Thomas D. PloS one. 2019; 14:e0225532.

Melgar, KM; Jones, LM; Walker, M; Bolanos, LC; Hueneman, K; Wunderlich, M; Jiang, J; Wilson, K; Zhang, X; Sutter, P; et al. Overcoming Adaptive Therapy Resistance in AML By Targeting Immune Response Pathways. Blood. 2019; 134:3934.

Wunderlich, M; Chen, J; O'Brien, E; Manning, N; Sexton, C; Byerly, L; Perentesis, JP; Mizukawa, B; Mulloy, JC. Global Gene Expression and Mutation Signatures Are Preserved in PDX Models of Pediatric AML and Aid Discovery of Targeted Therapy for Cases with CBFA2T3/GLIS2 Rearrangement. Blood. 2019; 134:3766.

Melgar, K; Walker, MM; Jones, LM; Bolanos, LC; Hueneman, K; Wunderlich, M; Jiang, J; Wilson, KM; Zhang, X; Sutter, P; et al. Overcoming adaptive therapy resistance in AML by targeting immune response pathways. Science Translational Medicine. 2019; 11:eaaw8828.

Tirtakusuma, R; Milne, P; Ptasinska, A; Meyer, C; Nakjang, S; Komkov, A; Williamson, D; Cauchy, P; Assi, S; Blair, H; et al. Epigenetic Regulator Genes Direct the Fate of Multipotent Progenitor Cell of Origin in Lineage Switched MLL-AF4 Leukaemia. 2019.

Li, Y; Xue, M; Deng, X; Dong, L; Nguyen, LX T; Ren, L; Han, L; Li, C; Xue, J; Zhao, Z; et al. TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal. Cell Stem Cell. 2023; 30:1072-1090.e10.

Bouffi, C; Wikenheiser-Brokamp, KA; Chaturvedi, P; Sundaram, N; Goddard, GR; Wunderlich, M; Brown, NE; Staab, JF; Latanich, R; Zachos, NC; et al. In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice. Nature Biotechnology. 2023; 41:824-831.

Liu, X; Sato, N; Yabushita, T; Li, J; Jia, Y; Tamura, M; Asada, S; Fujino, T; Fukushima, T; Yonezawa, T; et al. IMPDH inhibition activates TLR-VCAM1 pathway and suppresses the development of MLL-fusion leukemia. EMBO Molecular Medicine. 2023; 15:e15631.

Han, L; Dong, L; Leung, K; Zhao, Z; Li, Y; Gao, L; Chen, Z; Xue, J; Qing, Y; Li, W; et al. METTL16 drives leukemogenesis and leukemia stem cell self-renewal by reprogramming BCAA metabolism. Cell Stem Cell. 2023; 30:52-68.e13.

Weng, H; Huang, F; Yu, Z; Chen, Z; Prince, E; Kang, Y; Zhou, K; Li, W; Hu, J; Fu, C; et al. The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia. Cancer Cell. 2022; 40:1566-1582.e10.

Li, Y; Deng, X; Dong, L; Han, L; Nguyen, LX T; Xue, J; Zhao, Z; Li, W; Qing, Y; Shen, C; et al. TET2-Mediated mRNA and DNA Oxidation in Leukemia Homing and Immune Evasion. Blood. 2022; 140:2975-2977.

Tirtakusuma, R; Szoltysek, K; Milne, P; Grinev, VV; Ptasinska, A; Chin, PS; Meyer, C; Nakjang, S; Hehir-Kwa, JY; Williamson, D; et al. Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia. Blood. 2022; 140:1875-1890.

Barreyro, L; Sampson, AM; Ishikawa, C; Hueneman, KM; Choi, K; Pujato, MA; Chutipongtanate, S; Wyder, M; Haffey, WD; O'Brien, E; et al. Blocking UBE2N abrogates oncogenic immune signaling in acute myeloid leukemia. Science Translational Medicine. 2022; 14:eabb7695.

Wunderlich, M; Chen, J; Sexton, C; Manning, N; Byerly, L; O’Brien, E; Perentesis, J; Mulloy, J; Mizukawa, B. PDX models of relapsed pediatric AML preserve global gene expression patterns and reveal therapeutic targets. 2022; 2022.01.31.478534.

Zhao, H; Lu, J; Yan, T; Han, F; Sun, J; Yin, X; Chen, L; Shen, C; Wunderlich, M; Yun, W; et al. Opioid receptor signaling suppresses leukemia through both catalytic and non-catalytic functions of TET2. Cell Reports. 2022; 38:110253.

Fishman, H; Madiwale, S; Geron, I; Bari, V; Van Loocke, W; Kirschenbaum, Y; Ganmore, I; Kugler, E; Rein-Gil, A; Friedlander, G; et al. ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells. Blood. 2022; 139:399-412.

Earnest, KG; McConnell, EM; Hassan, EM; Wunderlich, M; Hosseinpour, B; Bono, BS; Chee, MJ; Mulloy, JC; Willmore, WG; DeRosa, MC; et al. Development and characterization of a DNA aptamer for MLL-AF9 expressing acute myeloid leukemia cells using whole cell-SELEX. Scientific Reports. 2021; 11:19174.

Wunderlich, M; Manning, N; Sexton, C; O’Brien, E; Byerly, L; Stillwell, C; Perentesis, JP; Mulloy, JC; Mizukawa, B. PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia. Frontiers in Oncology. 2021; 11:642466.

Wunderlich, M; Manning, N; O'Brien, E; Sexton, C; Byerly, L; Perentesis, JP; Mizukawa, B; Mulloy, JC. Abstract 5412: Xenograft based detection of rare leukemic clones in minimal residual disease negative diagnostic specimens from pediatric patients. Cancer Research. 2020; 80:5412.

Su, R; Dong, L; Li, Y; Gao, M; Han, L; Wunderlich, M; Deng, X; Li, H; Huang, Y; Gao, L; et al. Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion. Cancer Cell. 2020; 38:79-96.e11.

Rodriguez, S; Abundis, C; Boccalatte, F; Mehrotra, P; Chiang, MY; Yui, MA; Wang, L; Zhang, H; Zollman, A; Bonfim-Silva, R; et al. Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL. Leukemia. 2020; 34:1241-1252.

Khodoun, M; Peipp, M; Morris, SC; Angerman, E; Potter, C; Herr, A; Mulloy, J; Wunderlich, M; Finkelman, FD. Safe, rapid suppression of IgE-mediated allergy with monovalent (mv) anti-human (hu) FceRIa monoclonal antibody (mAb). Journal of immunology (Baltimore, Md. : 1950). 2020; 204:66.22.

Hinge, A; He, J; Bartram, J; Javier, J; Xu, J; Fjellman, E; Sesaki, H; Li, T; Yu, J; Wunderlich, M; et al. Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition. Cell Stem Cell. 2020; 26:420-430.e6.

Khodoun, MV; Morris, SC; Angerman, E; Potter, C; Schuman, R; Wunderlich, M; Maciag, JJ; Locker, KC S; Mulloy, JC; Herr, AB; et al. Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies. Journal of Allergy and Clinical Immunology. 2020; 145:907-921.e3.

Wunderlich, M; Manning, N; Sexton, C; Sabulski, A; Byerly, L; O'Brien, E; Perentesis, JP; Mizukawa, B; Mulloy, JC. Improved chemotherapy modeling with RAG-based immune deficient mice. Editor, Thomas D. PloS one. 2019; 14:e0225532.

Melgar, KM; Jones, LM; Walker, M; Bolanos, LC; Hueneman, K; Wunderlich, M; Jiang, J; Wilson, K; Zhang, X; Sutter, P; et al. Overcoming Adaptive Therapy Resistance in AML By Targeting Immune Response Pathways. Blood. 2019; 134:3934.

Wunderlich, M; Chen, J; O'Brien, E; Manning, N; Sexton, C; Byerly, L; Perentesis, JP; Mizukawa, B; Mulloy, JC. Global Gene Expression and Mutation Signatures Are Preserved in PDX Models of Pediatric AML and Aid Discovery of Targeted Therapy for Cases with CBFA2T3/GLIS2 Rearrangement. Blood. 2019; 134:3766.

Melgar, K; Walker, MM; Jones, LM; Bolanos, LC; Hueneman, K; Wunderlich, M; Jiang, J; Wilson, KM; Zhang, X; Sutter, P; et al. Overcoming adaptive therapy resistance in AML by targeting immune response pathways. Science Translational Medicine. 2019; 11:eaaw8828.

Tirtakusuma, R; Milne, P; Ptasinska, A; Meyer, C; Nakjang, S; Komkov, A; Williamson, D; Cauchy, P; Assi, S; Blair, H; et al. Epigenetic Regulator Genes Direct the Fate of Multipotent Progenitor Cell of Origin in Lineage Switched MLL-AF4 Leukaemia. 2019.

Huang, Y; Su, R; Sheng, Y; Dong, L; Dong, Z; Xu, H; Ni, T; Zhang, ZS; Zhang, T; Li, C; et al. Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia. Cancer Cell. 2019; 35:677-691.e10.

Goyama, S; Schibler, J; Mulloy, JC. Alternative translation initiation generates the N-terminal truncated form of RUNX1 that retains hematopoietic activity. Experimental Hematology. 2019; 72:27-35.

Contact Us

A photo of James Mulloy.

James Mulloy, PhD

Division of Experimental Hematology and Cancer Biology

Locations: S7.603

Phone: 513-636-1844

In the News

"James Mulloy, PhD, directs the Humanized Mouse Resource Core at Cincinnati Children’s, which worked for more than two years to generate a colony of immune-deficient mice that remain strong enough to grow and develop while carrying human forms of leukemia."

Read the entire article in Research Horizons.