Benjamin Huang, MD

Asst Professor in Residence
Primary Thematic Area
M_PEDS-ONCOLOGY
Secondary Thematic Area
Research Summary
Therapeutics and Functional Genomics in Hematologic Cancers

The research in our laboratory is focused on cancer modeling, molecular therapeutics, functional genomics, and biomarker discovery in hematologic cancers. Our research focuses primarily on pediatric acute myeloid leukemia (AML), which is characterized by frequent co-occurrence of fusion oncogenes and signal transduction mutations. While targeted inhibitors directed against either class of alteration have shown activity in AML, patients invariably relapse with treatment-refractory leukemia, underscoring the need for both a deeper understanding of how transcriptional and signaling mutations cooperate to drive leukemia growth and how these genetic alterations create novel dependencies. Thus, we are harnessing promising small molecule inhibitors and synthetic lethality approaches to uncover therapeutic vulnerabilities. We are also collaborating with the Children's Oncology Group (COG) to study the largest pediatric AML genome and transcriptome sequencing project to date (NCI TARGET). We are uncovering distinct transcriptional and epigenetic landscapes in pediatric AML, informing novel candidate biomarker signatures and immunotherapy targets. These data have also allowed us to achieve unprecedented residual disease detection using ultrasensitive molecular platforms in pediatric AML. Our overall goal is to develop new therapeutic and genomic strategies in AML to inform biology-driven, genetically stratified trials of innovative drug combinations.

Publications

Structural surfaceomics reveals an AML-specific conformation of integrin ß2 as a CAR T cellular therapy target.

Nature Cancer

Mandal K, Wicaksono G, Yu C, Adams JJ, Hoopmann MR, Temple WC, Izgutdina A, Escobar BP, Gorelik M, Ihling CH, Nix MA, Naik A, Xie WH, Hübner J, Rollins LA, Reid SM, Ramos E, Kasap C, Steri V, Serrano JAC, Salangsang F, Phojanakong P, McMillan M, Gavallos V, Leavitt AD, Logan AC, Rooney CM, Eyquem J, Sinz A, Huang BJ, Stieglitz E, Smith CC, Moritz RL, Sidhu SS, Huang L, Wiita AP

Pediatric Blood & Cancer

Clonally Related T-cell Malignancies and Hemophagocytic Lymphohistiocytosis in a Pediatric Patient

Meyer L, Huang I, Huang BJ, Steen E, Chung JH, Pawar A, Hermiston M, Ohgami R, Ruiz-Cordero R, Bhargava P, Marinoff A

Blood. American Society of Hematology

A Robust Long Non-Coding RNA Expression Classifier for Risk Stratification in Pediatric AML

Farrar JE, Smith JL, Othus M, Huang BJ, Wang Y-C, Ries RE, Hylkema TA, Pogosova-Agadjanyan EL, Challa S, Leonti AR, Shaw TI, Triche TJ, Gamis AS, Aplenc R, Kolb AE, Ma X, Stirewalt D, Alonzo TA, Meshinchi S

Blood. American Society of Hematology

Expanding the High-Risk Definition for Children with Newly Diagnosed Acute Myeloid Leukemia

Lamble AJ, Ries RE, Alonzo TA, Wang Y-C, Farrar JE, Huang BJ, Kutny MA, Pollard JA, Aplenc R, Gamis AS, Kolb EA, Cooper TM, Meshinchi S

Blood. American Society of Hematology

Structural Surfaceomics Reveals an AML-Specific Conformation of Integrin-β2 As an Immunotherapeutic Target

Mandal K, Wicaksono G, Yu C, Adams JJ, Hoopmann MR, Temple WC, Escobar BP, Gorelik M, Ihling C, Nix MA, Naik A, Ramos E, Kasap C, Steri V, Serrano JC, Salangsang F, Phojanakong P, McMillan M, Gavallos V, Leavitt AD, Sinz A, Huang BJ, Stieglitz E, Smith C, Moritz RL, Sidhu SS, Huang L, Wiita AP

Blood. American Society of Hematology

A Transcriptional Classifier Identifies Pediatric T-Cell Acute Lymphoblastic Leukemias at High Risk for End of Induction Minimal Residual Disease

Meyer LK, Roy RP, Pölönen P, Elsayed A, Huang BJ, Kimura S, Delgado-Martin C, Vincent TL, Ryan T, Wood BL, Chen Z, Liu Y, Zhang J, Horton TM, Loh ML, Devidas M, Raetz EA, Hayashi RJ, Winter SS, Dunsmore KP, Hunger SP, Pounds SB, Hermiston ML, Yang JJ, Mullighan CG, Teachey DT, Olshen AB

Blood. American Society of Hematology

Transcriptome Analysis and Machine Learning Prioritize Therapeutic Strategies for High-Risk Pediatric AML Patients of the KMT2A-Fusion Subgroup

Obermayer A, Yao S, Smith JL, Ries RE, Wang Y-C, Farrar JE, Furlan SN, Triche R, Ma X, Huang BJ, Wang X, Meshinchi S, Shaw TI

Cancer Research

Longitudinal monitoring of pediatric acute myeloid leukemia using duplex sequencing of patient-specific panels reveals ultra-low frequency MRD that marks persistent carcinogenesis and complex clonal evolution

Smith TH, Higgins JE, Lo FY, Hipp MJ, Valentine CC, Leonti AR, Ries RE, Meshinchi S, Huang BJ, Salk JJ

Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia.

Blood cancer discovery

Umeda M, Ma J, Huang BJ, Hagiwara K, Westover T, Abdelhamed S, Barajas JM, Thomas ME, Walsh MP, Song G, Tian L, Liu Y, Chen X, Kolekar P, Tran Q, Foy SG, Maciaszek JL, Kleist AB, Leonti AR, Ju B, Easton J, Wu H, Valentine V, Valentine MB, Liu YC, Ries RE, Smith JL, Parganas E, Iacobucci I, Hiltenbrand R, Miller J, Myers JR, Rampersaud E, Rahbarinia D, Rusch M, Wu G, Inaba H, Wang YC, Alonzo TA, Downing JR, Mullighan CG, Pounds S, Babu MM, Zhang J, Rubnitz JE, Meshinchi S, Ma X, Klco JM

Blood. American Society of Hematology

Integrated Genomic Analysis Identifies UBTF Tandem Duplications As a Subtype-Defining Lesion in Pediatric Acute Myeloid Leukemia

Umeda M, Ma J, Huang BJ, Hagiwara K, Westover T, Abdelhamed S, Barajas JM, Thomas ME, Walsh MP, Song G, Tian L, Liu Y, Chen X, Kolekar P, Tran Q, Foy S, Maciaszek JL, Kleist AB, Leonti AR, Ju B, Easton J, Wu H, Valentine V, Valentine M, Liu Y-C, Ries RE, Smith JL, Parganas E, Iacobucci I, Hiltenbrand R, Miller J, Myers J, Rampersaud E, Rahbarinia D, Rusch M, Wu G, Inaba H, Wang Y-C, Alonzo TA, Downing JR, Mullighan CG, Pounds SB, Babu MM, Zhang J, Rubnitz JE, Meshinchi S, Ma X, Klco JM

Blood. American Society of Hematology

EZH2-Mediated MHC Class II Silencing Drives Immune Evasion in AML with t(16;21) FUS-ERG

Buteyn NJ, Burke CG, Smith JL, Ries RE, Leonti AR, Shaw TI, Huang BJ, Alonzo TA, Furlan SN, Farrar JE, Meshinchi S, Triche TJ

Blood. American Society of Hematology

Integrated Transcriptomics and Proteomics Identifies Therapeutic Targets in Pediatric Acute Myeloid Leukemia

Huang BJ, Smith JL, Shaw TI, Furlan SN, Ries RE, Leonti AR, Crowgey EL, Wei L, Farrar JE, Triche T, Ma X, Le Q, Meshinchi S

Blood. American Society of Hematology

Targeting FOLR1 in High-Risk CBF2AT3-GLIS2 AML with Stro-002 FOLR1-Directed Antibody-Drug Conjugate

Le Q, Smith JL, Tang TT, Castro S, Nourigat-Mckay C, Perkins L, Huang BJ, Ries RE, Leonti AR, Hylkema TA, Pardo L, Abrahams C, Bedard K, Molina A, Eidenschink Brodersen L, Loken MR, Meshinchi S

Blood. American Society of Hematology

ETS Family Transcription Factor Fusions in Childhood AML: Distinct Expression Networks and Clinical Implications

Smith JL, Ries RE, Wang Y-C, Leonti AR, Alonzo TA, Gamis AS, Aplenc R, Kolb AE, Huang BJ, Ma X, Shaw TI, Meshinchi S

Journal of Clinical Oncology

Targeted gene expression classifier identifies pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients at high risk for end induction minimal residual disease positivity

Meyer LK, Roy R, Huang BJ, Delgado-Martin C, Vincent TL, Wood BL, Liu Y, Zhang J, Mullighan CG, Horton TM, Loh ML, Devidas M, Raetz EA, Hayashi RJ, Winter SS, Dunsmore KP, Hunger S, Teachey DT, Olshen AB Hermiston ML

Leukemia Research

A Targeted Gene Expression Classifier Identifies Pediatric T-ALL Patient at High Risk for End Induction Minimal Residual Disease Positivity

Meyer L, Roy RP, Huang BJ, Kimura S, Polonen P, Delgado-Martin C, Vincent T, Ryan T, Wood B, Liu Y, Zhang J, Mullighan C, Horton T, Loh M, Devidas M, Raetz E, Hayashi R, Winter S, Dunsmore K, Hunger S, Teachey D, Hermiston M, Olshen AB

Blood. American Society of Hematology

Duplex Sequencing with Patient-Specific Hybrid Capture Panels Reveals Ultra-Low Frequency Measurable Residual Disease in Pediatric Acute Myeloid Leukemia

Higgins J, Lo FY, Hipp MJ, Valentine CC, Williams LN, Leonti AR, Ries RE, Radich JP, Meshinchi S, Huang BJ, Salk JJ

Blood. American Society of Hematology

Integrated Stem Cell Signature and Cytomolecular Risk Determination in Pediatric Acute Myeloid Leukemia

Huang BJ, Smith JL, Ries RE, Leonti AR, Crowgey EL, Furlan SN, Shaw T, Wei L, Wang Y-C, Gerbing RB, Alonzo TA, Cooper TM, Kolb EA, Ma X, Farrar JE, Triche TJ, Meshinchi S

Blood. American Society of Hematology

Co-Targeting BET Bromodomain Proteins and Aberrant Signaling in AML

Huang BJ, Wang X, Harris M, Wandler A, Hwang E, Burgess MR, Li Q, Severson P, Powell B, Kolb EA, Meshinchi S, Taylor BS, Bollag G, Shannon KM

Blood. American Society of Hematology

Genome and Transcriptome Profiling of Monosomy 7 AML Defines Novel Risk and Therapeutic Cohorts

Ries RE, Triche TJ, Smith JL, Leonti AR, Alonzo TA, Farrar JE, Chen X, Liu Y, Shaw T, Huang BJ, Wang Y-C, Gerbing RB, Hirsch BA, Raimondi SC, Gamis AS, Aplenc R, Zhang J, Kolb EA, Ma X, Meshinchi S

Journal of Clinical Oncology. American Society of Clinical Oncology

Gene expression signature associated with in vitro dexamethasone resistance and post-induction minimal residual disease in pediatric T-cell acute lymphoblastic leukemia

Meyer LK, Delgado-Martin C, Roy R, Huang BJ, Vincent T, Olshen A, Wood BL, Liu Y, Zhang J, Mullighan CG, Horton TM, Loh ML, Devidas M, Raetz EA, Hayashi RJ, Winter S, Dunsmore KP, Hunger S, Teachey DT, Hermiston HL

Blood. American Society of Hematology

Glucocorticoids Paradoxically Induce Intrinsic Steroid Resistance through a STAT5-Mediated Survival Mechanism in T-Cell Acute Lymphoblastic Leukemia

Meyer LK, Huang BJ, Roy R, Hechmer A, Wandler A, Delgado-Martin C, Olshen AB, Horton TM, Teachey DT, Shannon KM, Hermiston ML

British Journal of Haematology

Glucocorticoids paradoxically induce steroid resistance through a STAT5-mediated survival mechanism in T-cell acute lymphoblastic leukemia/lymphoma

Meyer LK, Delgado-Martin C, Huang BJ, Wandler AM, Horton TM, Teachey DT, Shannon KM, Hermiston ML

Blood. American Society of Hematology

Response and Resistance to Bromodomain Inhibition in AML Driven By Hyperactive Ras Signaling

Huang BJ, Hwang E, Wandler AM, Powell B, Bollag G, Shannon K

Blood. American Society of Hematology

Resistant T-Cell Acute Lymphoblastic Leukemias That Emerge after In Vivo Treatment with Dexamethasone Frequently Down-Regulate Glucocorticoid Receptor Protein Expression

Wandler AM, Huang B, Scacchetti A, Craig J, Yan H, Monsalve G, Li Q, Dail M, Wong JC, Nakitandwe J, Weinberg O, Hasserjian RP, Kogan SC, Sampath D, Downing JR, Yamamoto K, Taylor BS, Aster JC, Zhang J, Shannon K

Blood. American Society of Hematology

Risk Factors for Graft Failure with Busulfan/Fludarabine-Based Conditioning in Children Undergoing Allogeneic Hematopoietic Cell Transplantation for Nonmalignant Disorders

Huang BJ, Dvorak CC, Wahlstrom J, Hwang J, Long-Boyle JR, Cowan MJ, Horn BN

Blood. American Society of Hematology

Expressing N-Ras(G12D) from the endogenous promoter induces myeloproliferative disease (MPD) and cooperates with retroviral insertional mutagenesis (RIM) to generate acute myeloid leukemia (AML)

Li Q, Haigis K, McDaniel A, Huang BJ, Miller M, Shieh A, Kogan S, Wolff L, Jacks T, Shannon K