Alan Williams, Ph.D.
Fate Therapeutics
San Diego,CA
2027
years of professional experience
Work History
Principal Scientist, Pre-Clinical
3 Years 2 Months- Led a team of two PhD research scientists for implementation and functional testing of immune evasion strategies including an alloimmune defense receptor (ADR) and genetic ablation of an adhesion ligand (CD58KO) in an iPSC-derived CAR T-cell platform.
- Worked cross-functionally with colleagues to test and implement immune evasion strategies across product platforms (CD38 conditioning, CD47 and HLA-E over-expression, and MHC-I/II genetic ablation), including collaborations with ONO Pharmaceuticals, to deliver iPSC-derived CAR T cells without conditioning chemotherapy.
- Assay development and research led to IND enabling work for FT836, a CAR T cell therapy targeting MICA/B which incorporates ADR and CD58KO for treatment of solid tumor indications, and delivery of the product without conditioning chemotherapy. Clinical trial number NCT07216105.
Senior Scientist, Cancer Immunotherapy
2 Years- Oversaw implementation of a novel alloimmune defense receptor (ADR) into an iPSC-derived CAR NK cell platform for depletion of alloreactive immune cell subsets.
- Directed a team of research scientists, including three PhDs and one MS, during a collaboration with Janssen Pharmaceuticals (Johnson & Johnson Innovative Medicine) to explore immune evasion strategies in iPSC-derived CAR NK cells.
- Generated Investigational New Drug (IND) enabling datasets for incorporation of ADR in FT522, an NK cell therapy to undergo phase I clinical trial evaluation for treatment of autoimmune disease.
Scientist, Cancer Immunotherapy
2 Years 1 Month- Pioneered my team's efforts for in vitro testing of human iPSC derived CAR T-cell phenotypes, expansion, and effector functions.
- Pioneering a lentivirally based platform for the rapid introduction and testing of persistence edits in human iPSC derived CAR T- cells.
Postdoctoral Fellow-Immunology/Protein And Cell Engineering
2 Years 4 Months- Led a project with the goal of engineering CAR T cells at both the genetic and protein levels to improve their persistence in allogeneic settings as well as developing strategies for efficient multiplex genome editing of CAR T-cells. Responsible for compiling reports of the generated data for both internal use and for inclusion in an IND filing for a CAR T-cell therapeutic attribute. My work has been highlighted in publications including co-first authorship of a Nature Communications publication and I have been honored by the STAT news editorial staff as a 2018 Wunderkind. "The 2018 STAT Wunderkinds honors the brightest young minds in life science for their work in academia, industry, and in the clinic." https://www.statnews.com/wunderkinds/
Doctoral/Postdoctoral Research Scientist
- Discovered the transcription factor B cell lymphoma 6 (Bcl6), in an immortalized B cell line, is required for the molecular mechanism of immunoglobulin gene somatic hypermutation and gene conversion
- The first to describe (in the hypermutating DT40 B cell line) a Bcl6 -dependent alteration in transcriptional parameters important for immunoglobulin gene mutation by utilizing chromatin immunoprecipitation and next generation sequencing
- Trained both graduate and undergraduate students in research methods while supervising their specific projects; organized and conducted recitation sessions for an undergraduate introductory biology class
- Awarded National Science Foundation Graduate Research Fellowship (accepted) and Ford Foundation Pre-Doctoral Fellowship (declined)
Education
Ph.D. - Immunobiology
- Dissertation: "Bcl6 is Required for Somatic Hypermutation and Gene Conversion in DT40 Cells." Advisor: Dr. David Schatz
Bachelor of Science - Microbiology
- Magna cum laude
Skills
Protein and cellular engineering of Chimeric Antigen Receptor (CAR) T cells and iPSC derived human CAR T cells and subsequent phenotyping/profiling
Expertise in PBMC cell culture and assays for the generation of primed effector T cells against allogeneic target CAR T cells (Mixed lymphocyte reactions (MLR))
In-vivo injection (mouse models) of lymphodepleting chemotherapeutic regents
antibodies
and lymphocytes (human and murine). Isolation of injected lymphocytes from blood
spleen
and bone marrow for flow cytometry analysis
Expertise in NSG and immune competent mouse models to assess CAR T- cell anti-tumor activity and persistence/immune evasion in allogeneic settings in vivo
Expertise in T- and NK-cell diversity
effector functions
and mechanisms for inhibiting effector functions to improve the immune-evasive properties of allogeneic CAR T-cell products
Flow cytometry and luminescence based assays for assessing human iPSC derived CAR T cell and human/murine CAR T cell effector functions
anti-tumor cytotoxicity
and proliferation
Expertise in T-cell allogeneic responses
identifying clonal restriction
and leveraging insights for studies investigating immune synapse formation and specificity of T-cell reactivity
Assays for the expansion of NK cells and assessment of NK-cell cytotoxicity against allogeneic CAR T cells
Expertise in B cell biology including mechanisms of antibody diversification
B cell isolation and in vitro culture/stimulation
and autoreactive B cell targeting including SLE patient derived samples
Assays for antibody mediated effector function including ADCC and CDC in vitro and in vivo
Over 18 years of multi-color flow cytometry experience including BD instruments (Fortessa X-20/Symphony)
Cytoflex
and flowjo analysis software
RNA transfection
viral preparation
and transduction of primary human and murine lymphocytes
Extensive experience with retroviral
lentiviral
and homology driven targeted integration based gene delivery and expression in mammalian cells including mouse and human primary cells
Expertise in TALEN and Crispr/Cas9 based gene-editing of human and murine T cells
Execution of Next-Gen sequencing assays designed to assess off-targeting effects of gene-editing nucleases
Molecular biology techniques including ELISA
DNA cloning
RT-PCR
QPCR
in vitro RNA synthesis
and SDS-PAGE/western blotting
Timeline
Principal Scientist, Pre-Clinical
Fate Therapeutics
02.2023 - 04.2026Read More
Senior Scientist, Cancer Immunotherapy
Fate Therapeutics
02.2021 - 02.2023Read More
Scientist, Cancer Immunotherapy
Fate Therapeutics Inc.
01.2019 - 02.2021Read More
Postdoctoral Fellow-Immunology/Protein And Cell Engineering
Cellectis
08.2016 - 12.2018Read More
Louisiana State University
Bachelor of Science from Microbiology
Read More
Yale University
Ph.D. from Immunobiology
Read More
Doctoral/Postdoctoral Research Scientist
Yale University
7 2008 - 2016Read More
Publications
Hammer Q, Perica K, Mbofung RM, van Ooijen H, Martin KE, Momayyezi P, Varady E, Pan Y, Jelcic M, Groff B, Abujarour R, Krokeide SZ, Lee T, Williams A, Goodridge JP, Valamehr B, Önfelt B, Sadelain M, Malmberg KJ. Genetic ablation of adhesion ligands mitigates rejection of allogeneic cellular immunotherapies. Cell Stem Cell. 2024 Sep 5;31(9):1376-1386.e8. doi: 10.1016/j.stem.2024.06.011. Epub 2024 Jul 8. PMID: 38981470; PMCID: PMC12718542.
Jo S, Das S, Williams A, Chretien AS, Pagliardini T, Le Roy A, Fernandez JP, Le Clerre D, Jahangiri B, Chion-Sotinel I, Rozlan S, Dessez E, Gouble A, Dusséaux M, Galetto R, Duclert A, Marcenaro E, Devillier R, Olive D, Duchateau P, Poirot L, Valton J. Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing. Nat Commun. 2022 Jun 30;13(1):3453. doi: 10.1038/s41467-022-30896-2. PMID: 35773273; PMCID: PMC9247096. (co-first author)
Sachdeva M, Busser BW, Temburni S, Jahangiri B, Gautron AS, Maréchal A, Juillerat A, Williams A, Depil S, Duchateau P, Poirot L, Valton J. Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality. Nat Commun. 2019 Nov 13;10(1):5100. doi: 10.1038/s41467-019-13088-3. Erratum in: Nat Commun. 2020 May 7;11(1):2357. doi: 10.1038/s41467-020-16301-w. PMID: 31723132; PMCID: PMC6853973.
Williams AM, Maman Y, Alinikula J, Schatz DG. Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells. PLoS One. 2016 Feb 22;11(2):e0149146. doi: 10.1371/journal.pone.0149146. PMID: 26900682; PMCID: PMC4762950. (first author)
Xiao L, Williams AM, Grove A. The C-terminal domain of yeast high mobility group protein HMO1 mediates lateral protein accretion and in-phase DNA bending. Biochemistry. 2010 May 18;49(19):4051-9. doi: 10.1021/bi1003603. PMID: 20402481.
Grants, Honors, and Recent Conferences
- 2010 National Science Foundation Graduate Research Fellowship (accepted)
- 2010 Ford Foundation Pre-Doctoral Fellowship (declined)
- Abstract No. 336. Alloimmune Defense Receptor with Genetic Ablation of Adhesion Ligand CD58 Promotes Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy. Williams, Alan*, et. al. Society for Immunotherapy of Cancer Annual Meeting. 2024. Presenting Author
- Abstract No. 503. Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 Is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy. American Society of Hematology Annual Meeting. 2004. Williams, Alan* et. al. Presenting Author/Oral Presentation