Medical Director, GMP Facility, Sue and Bill Gross Stem Cell Research Center

Associate Professor of Clinical Medicine (Hematology/Oncology)
School of Medicine

developmental therapeutics; hematologic malignancies; cell and gene therapy; early clinical development; hematopoietic stem cell biology; cancer biology; cell cycle regulation

ORCID page

As Medical Director for UCI’s Good Manufacturing Practice (GMP) facility that conducts clinical manufacturing of investigational cell and gene therapies, I will represent UCI in its participation in the California Institute for Regenerative Medicine (CIRM) cGMP facility infrastructure network. In this capacity, my goal is to support and enhance investigator-initiated clinical trials of FDA-regulated cell and gene therapies by leveraging expertise and experience in clinical drug development. My initial research objective is to collaborate with other UCI faculty to facilitate translation of high impact preclinical findings with potential to address unmet clinical needs into trials of regenerative medicine technologies aligned with institutional strengths and priorities. I will also work to develop academic-industry partnerships to establish a long-term sustainable pipeline for cGMP facility operations. Within my clinical role as part of the Division of Hematology/Oncology, I aim to contribute to existing strengths of the division in clinical research in hematologic malignancies, specifically acute leukemias.

American Society of Hematology Junior Faculty Scholar, 2008-2010
Leukemia Research Foundation New Investigator Award, 2008-2009
Sidney Kimmel Foundation for Cancer Research Scholar, 2009-2012
American Cancer Society (ACS) Research Scholar, 2012-2016

I am a physician-scientist with over 20 years of professional experience following completion of clinical training in oncology and postdoctoral studies in cancer biology. Through 2017, I ran an independent research laboratory focused on studying the interplay between control of the cell division cycle and molecular mechanisms of cancer. The overarching objective of my work was to understand how loss of the tumor suppressor functions of the ubiquitin-proteasome system regulating the cell cycle contributes to cancer. My laboratory heavily utilized murine models to study hematopoiesis and hematopoietic stem cell function in vivo.

I transitioned to the biopharmaceutical industry in 2017. My industry work drew from my prior clinical and research expertise in academia and focused initially on development of early phase clinical studies as part of investigational new drug submissions (INDs) for hematologic malignancies. In my second industry position at an early clinical-stage biotechnology company aimed at utilizing CRISPR-Cas base editor technology to develop potentially curative therapies for life-threatening illnesses, I played a major role in moving two pre-clinical programs into proof-of-concept clinical trials: an ex vivo gene-edited, autologous hematopoietic stem cell-based investigational therapy for patients with sickle cell anemia and an allogeneic, multiplex gene-edited CAR-T therapy for patients with T-cell acute lymphoblastic leukemia/lymphoma.

Selected Publications:

Minella AC, Loeb KR, Knecht A, Welcker M, Varnum-Finney B, Bernstein ID, Roberts JM, Clurman BE. Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo. Genes and Development. 2008 Jun 15;22(12):1677-89. PMCID: PMC2428064

Xu Y, Sengupta T, Kukreja L, Minella AC. MicroRNA-223 Regulates Cyclin E Activity by Modulating Expression of F-Box and WD-40 Domain Protein 7. J Biol Chem. 2010 Nov 5;285(45):34439-46. PMCID: PMC2966058

Sengupta T, Abraham G, Xu, Y, Clurman BE, Minella AC. Hypoxia inducible factor-1 is activated by dysregulated cyclin E during mammary epithelial morphogenesis. Mol Cell Biol. 2011 Sept: 3885-95.
PMCID: PMC3165725

Siu KT, Rosner MR, Minella AC. An integrated view of cyclin E function and regulation. Cell Cycle. 2012 Jan 1: 1, 57-64. PMCID: PMC3272232

Xu Y, Bhattacharyya M, Swartz K, Siu KT, Minella AC. Fbw7-dependent cyclin E regulation ensures terminal maturation of murine bone marrow erythroid cells by restraining oxidative metabolism. Oncogene. 2013 Jul 22. doi: 10.1038/onc.2013.289. PMCID: PMC3939062

Olive V, Sabio E, Bennett M, De Jong CS, Biton A, Walker J, Greaney SK, Sodir NM, Zhou AY, Balakrishnan A, Foth M, Luftig MA, Goga A, Speed TP, Xuan Z, Evan GI, Minella AC, and He L. A component of the polycistronic mir-17-92 oncomir promotes oncogene-dependent apoptosis. Elife. 2013 Oct 15;2:e00822. PMCID: PMC3796314

Siu KT, Xu Y, Swartz KL, Bhattacharyya M, Gurbuxani S, Hua Y, Minella AC. Chromosome instability underlies hematopoietic stem cell dysfunction and lymphoid neoplasia associated with impaired Fbw7-
mediated cyclin E regulation. Mol Cell Biol. 2014 Sept: 3244-58. PMCID: PMC4135554

Siu K and Minella AC. Developing a systems-based understanding of hematopoietic stem cell cycle control. Adv Exp Med Biol. 2014; 844:189-200. PMID: 25480642

Olive V, Minella AC, He L. Outside the coding genome, mammalian microRNAs confer structural and functional complexity. Science Signaling. 2015 Mar 17. PMCID: PMC4425368

Mitzelfelt KA, Limphong P, Choi MJ, Kondrat FD, Lai S, Kolander KD, Kwok WM, Dai Q, Grzybowski MN, Zhang H, Taylor GM, Lui Q, Thao MT, Hudson JA, Barresi R, Bushby K, Jungbluth H, Wraige E, Geurts AM, Benesch JL, Riedel M, Christians ES, Minella AC, Benjamin IJ. The Human 343delT HSPB5 Chaperone Associated with Early-onset Skeletal Myopathy Causes Defects in Protein Solubility. J Biol Chem. 2016 Jul 15;291(29):14939-53. PMID: 27226619

Swartz KL, Wood SN, Murthy T, Martinez O, Qin G, Pillai MM, Rao S, and Minella AC. E2F-2 promotes nuclear condensation and enucleation of terminally differentiated erythroblasts. Mol Cell Biol. 2016 Dec 19;37(1). PMCID: PMC5192079

Kesarwani AK, Ramirez O, Gupta AK, Yang X, Murthy T, Minella AC, and Pillai MM. Cancer associated SF3B1 mutants recognize otherwise inaccessible cryptic 3’ splice sites within RNA secondary
structures. Oncogene. 2017 Feb 23;36(8):1123-1133. PMID: 27524419

Murthy T, Bluemn T, Gupta AK, Reimer M Jr, Rao S, Pillai MM*, Minella AC*. Cyclin-dependent kinase 1 (CDK1) and CDK2 have opposing roles in regulating interactions of splicing factor 3B1 with chromatin.
J Biol Chem. 2018 Jun 29; 293(26):10220-10234. PMCID: PMC6028971 *co-corresponding authors

Gupta AK, Murthy T, Paul KV, Ramirez O, Fisher JB, Rao S, Rosenberg AB, Seelig G, Minella AC*, and Pillai MM*. Degenerate minigene library analysis enables identification of altered branch point choice by
mutant splicing factor 3B1 (SF3B1). Nucleic Acids Res., 2019 Jan 25;47(2):970-980. PMCID: PMC6344872 *co-corresponding authors

Murthy T, Paul KV, Minella AC, and Pillai MM. The development and use of scalable systems for studying aberrant splicing in SF3B1-mutant CLL. Methods Mol Biol., 2019; 1881:83-99. PMID: 30350199

Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, Krönke J, Facon T, Salnikov AV, Lesley R, Beutner K, Kalabus J, Rasmussen E, Riemann K, Minella AC, Munzert G, Einsele H. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol., 2020 Mar 10;38(8):775-783. PMID: 31895611

Meyer AE, Furumo F, Stelloh C, Minella AC, Rao S. Loss of Fbxw7 triggers mammary tumorigenesis associated with E2F/c-Myc activation and Trp53 mutation. Neoplasia. 2020 Nov; 22(11): 644-658. PMID: 33070870

Rees HA, Minella AC, Burnett CA, Komor AC, and Gaudelli NM. CRISPR-derived genome editing therapies: Progress from bench to bedside. Mol. Ther. 2021 Nov 3;29(11):3125-3139. PMCID: PMC8572140.

American Society of Hematology (Sci Committee Chair, 2016)

Internal Medicine Residency (ABIM Research Pathway)
University of Washington School of Medicine 1998—2000

Clinical Oncology Fellowship
University of Washington and Fred Hutchinson Cancer Research Center 2000—2004

Postdoctoral Fellowship
Fred Hutchinson Cancer Research Center 2001—2006

Biopharmaceutical Company Roles: Early Development Lead; Hematologic malignancies early portfolio lead
Amgen 2017—2020

Vice President, Hematology/Oncology Clinical Development
Beam Therapeutics 2020—2024

Link to this profile
https://faculty.uci.edu/profile/?facultyId=7269

Last updated
10/13/2024