Bio

I am currently a postdoctoral fellow with Dr. Max Krummel at UCSF studying antigen uptake and transfer. As of September 2023, I am a co-organizer for Black in Immuno.

I completed my PhD in Immunology with Dr. Ravi Majeti at Stanford University, where I investigated the role of inflammation in acute myeloid leukemia progression in the context of inherited blood disorders and as it relates to chemotherapy resistance and disease relapse. Prior to being in the San Francisco Bay Area, I attended school and worked in Cambridge, MA. I received my B.S. in biology with a minor in Asian diaspora studies from MIT, where I spent the majority of my time studying the behavior of metastasizing cancer cells and the global Chinese diaspora. After graduating in 2015, I worked on untangling host-pathogen biology using single-cell RNA-Seq at the Broad Institute.

You can contact me at amy [dot] fan [at] ucsf [dot] edu.

Honors & Awards

  • Amgen Scholar, Amgen Foundation (Jun - Aug 2014)
  • Gene Brown Prize for Teaching, MIT Department of Biology (June 2015)
  • Stanford Graduate Fellowship, Stanford University (September 2016)
  • NSF Graduate Research Fellowship, National Science Foundation (March 2017)
  • Stanford Biosciences Travel Grant, Stanford Biosciences (Aug 2018)
  • Excellence in Advocacy, Stanford Diversity & Advocacy Committee (May 2019)
  • Community Impact Award, Stanford Alumni Association (May 2019)
  • Excellence in Service to Grad Students, Stanford Biosciences (June 2019)
  • Best Graduate Student Talk, Stanford Immunology (November 2020)
  • ASH Abstract Achievement Award, American Society of Hematology (November 2020)
  • Gerald J. Lieberman Fellowship, Stanford University (May 2021)
  • James W. Lyons Award, Stanford University (May 2021)
  • Experimental Hematology Travel Grant, ISEH (August 2021)

Professional Affiliations and Activities

  • Member, International Society of Experimental Hematology (2018 - Present)

Membership Organizations

Education & Certifications

  • BS, Massachusetts Institute of Technology, Biology (2015)

Contact

  • Academic
    amyfan@stanford.edu
    University - Student Department: School of Medicine - IDP's - Immunology Position: Graduate

Additional Info

Links

Current Research and Scholarly Interests

Germline mutations in RUNX1 cause an autosomal dominant disorder characterized by lifelong thrombocytopenia and increased risk of progression to acute myeloid leukemia (AML). Indeed, unlike sporadic AML, which commonly presents in the elderly, the average age of onset for RUNX1 familial AML cases is 35, with over one-third of patients developing leukemia as a child. While megakaryocyte defects have been shown to be a cell-autonomous effect of RUNX1 mutations in hematopoietic stem and progenitor cells (HSPCs), the mechanisms by which germline RUNX1 mutations progress to leukemia remains unclear. Interestingly, RUNX1 is also expressed in bone marrow mesenchymal stromal cells (BM-MSCs), which have been shown to contribute to the pathogenesis of some hematopoietic malignancies. The goal of my thesis research is to determine how RUNX1 mutations may be contributing to leukemogenesis through both cell autonomous and non-autonomous mechanisms.

Lab Affiliations

Work Experience

  • Academic Research Technician, Broad Institute of MIT & Harvard (January 2015 - May 2016)

    Investigate how heterogeneous regulation of LPS modifications by PhoPQ and PmrAB in S. Typhimurium modulate Type I IFN response in mouse macrophages. Developed single-cell RNA-Seq method to simultaneously probe host and pathogen transcriptomes.

    Location

    Cambridge, MA

All Publications

  • RUNX1 loss renders hematopoietic and leukemic cells dependent on interleukin-3 and sensitive to JAK inhibition. The Journal of clinical investigation Fan, A. C., Nakauchi, Y., Bai, L., Azizi, A., Nuno, K. A., Zhao, F., Köhnke, T., Karigane, D., Cruz-Hernandez, D., Reinisch, A., Khatri, P., Majeti, R. 2023

    Abstract

    Disease-initiating mutations in the transcription factor RUNX1 occur as germline and somatic events that cause leukemias with particularly poor prognosis. However, the role of RUNX1 in leukemogenesis is not fully understood and effective therapies for RUNX1-mutant leukemias remain elusive. Here, we use primary patient samples and a RUNX1 knockout model in primary human hematopoietic cells to investigate how RUNX1 loss contributes to leukemic progression and to identify targetable vulnerabilities. Surprisingly, we found that RUNX1 loss decreased proliferative capacity and stem cell function. However, RUNX1-deficient cells selectively upregulated the interleukin-3 (IL-3) receptor. Exposure to IL-3, but not other JAK/STAT cytokines, rescued RUNX1 KO proliferative and competitive defects. Further, we demonstrated that RUNX1 loss repressed JAK/STAT signaling and rendered RUNX1-deficient cells sensitive to JAK inhibitors. Our study identifies a dependency of RUNX1-mutant leukemias on IL-3/JAK/STAT signaling, which may enable these aggressive blood cancers to be targeted with existing agents.

    View details for DOI 10.1172/JCI167053

    View details for PubMedID 37581927

  • Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy. Cancer discovery Linde, M. H., Fan, A. C., Kohnke, T., Trotman-Grant, A. C., Gurev, S. F., Phan, P., Zhao, F., Haddock, N. L., Nuno, K. A., Gars, E. J., Stafford, M., Marshall, P. L., Dove, C. G., Linde, I. L., Landberg, N., Miller, L. P., Majzner, R. G., Zhang, T. Y., Majeti, R. 2023

    Abstract

    Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) and eradicating malignant cells. Here, we present a cancer vaccination approach utilizing myeloid lineage reprogramming to directly convert cancer cells into tumor reprogrammed-antigen presenting cells (TR-APCs). Using syngeneic murine leukemia models, we demonstrate that TR-APCs acquire both myeloid phenotype and function, process and present endogenous TAAs, and potently stimulate TAA-specific CD4+ and CD8+ T cells. In vivo TR-APC induction elicits clonal expansion of cancer-specific T cells, establishes cancer-specific immune memory, and ultimately promotes leukemia eradication. We further show that both hematologic cancers and solid tumors, including sarcomas and carcinomas, are amenable to myeloid-lineage reprogramming into TR-APCs. Finally, we demonstrate the clinical applicability of this approach by generating TR-APCs from primary clinical specimens and stimulating autologous patient-derived T cells. Thus, TR-APCs represent a cancer vaccination therapeutic strategy with broad implications for clinical immuno-oncology.

    View details for DOI 10.1158/2159-8290.CD-21-0502

    View details for PubMedID 36856575

  • Targeting IDH1-Mutated Pre-Leukemic Hematopoietic Stem Cells in Myeloid Disease, Including CCUS and AML Landberg, N., Koehnke, T., Nakauchi, Y., Fan, A., Karigane, D., Thomas, D., Majeti, R. AMER SOC HEMATOLOGY. 2022: 2234-2235

    View details for DOI 10.1182/blood-2022-159617

    View details for Web of Science ID 000893223202103

  • The cell type specific 5hmC landscape and dynamics of healthy human hematopoiesis and TET2-mutant pre-leukemia. Blood cancer discovery Nakauchi, Y., Azizi, A., Thomas, D., Corces, M. R., Reinisch, A., Sharma, R., Cruz Hernandez, D., Kohnke, T., Karigane, D., Fan, A., Martinez-Krams, D., Stafford, M., Kaur, S., Dutta, R., Phan, P., Ediriwickrema, A., McCarthy, E., Ning, Y., Phillips, T., Ellison, C. K., Guler, G. D., Bergamaschi, A., Ku, C., Levy, S., Majeti, R. 2022

    Abstract

    The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that is mediated by ten-eleven-translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape of normal hematopoiesis and identify cell type-specific 5hmC profiles associated with active transcription and chromatin accessibility of key hematopoietic regulators. We utilized CRISPR/Cas9 to model TET2 loss-of-function mutations in primary human HSPCs. Disrupted cells exhibited increased colonies in serial replating, defective erythroid/megakaryocytic differentiation, and in vivo competitive advantage and myeloid skewing coupled with reduction of 5hmC at erythroid-associated gene loci. Azacitidine and ascorbate restored 5hmC abundance and slowed or reverted the expansion of TET2-mutant clones in vivo. These results demonstrate the key role of 5hmC in normal hematopoiesis and TET2-mutant phenotypes and raise the possibility of utilizing these agents to further our understanding of pre-leukemia/clonal hematopoiesis.

    View details for DOI 10.1158/2643-3230.BCD-21-0143

    View details for PubMedID 35532363

  • IL-3 SELECTIVELY RESCUES RUNX1-DEFICIENT HUMAN HSPCS WITH DYSREGULATED JAK/ STAT SIGNALING Fan, A., Azizi, A., Nuno, K., Nakauchi, Y., Zhao, F., Cruz-Hernandez, D., Reinisch, A., Majeti, R. ELSEVIER SCIENCE INC. 2022: S84

    View details for Web of Science ID 000890643400129

  • Black In Immuno: harnessing social media and digital platforms to connect the dots. Nature reviews. Immunology Babdor, J., Fan, A. C., Wane, M., Mbiribindi, B., Mobley, A. S., Noel, J. C., Kouame, E. 2021

    View details for DOI 10.1038/s41577-021-00645-5

    View details for PubMedID 34744170

  • Black in Immuno Week: Who We Are, What We Did, and Why It Matters. Journal of immunology (Baltimore, Md. : 1950) Kouame, E., Noel, J. C., Wane, M., Babdor, J., Caslin, H. L., Fan, A., Mbiribindi, B., Sattler, S., Mobley, A. S. 2021; 207 (8): 1941-1947

    Abstract

    Our organization, Black in Immuno (@BlackInImmuno), was formed in September 2020 to celebrate, support, and amplify Black voices in immunology when social media campaigns like #BlackInTheIvory illuminated the shared overt and covert issues of systemic racism faced by Black researchers in all facets of science, technology, engineering, art, and mathematics. Black in Immuno was cofounded by a group of Black immunology trainees working at multiple institutions globally: Joel Babdor, E. Evonne Jean, Elaine Kouame, Alexis S. Mobley, Justine C. Noel, and Madina Wane. We devised Black in Immuno Week, held November 22-28, 2020, as a global celebration of Black immunologists. The week was designed to advocate for increased diversity and accessibility in immunology, amplify Black excellence in immunology, and create a community of Black immunologists who can support each other to flourish despite barriers in academia and other job sectors. The week contained live panels and scientific talks, a casual networking mixer, online advocacy and amplification sessions, and a series of wellness events. Our live-streamed programs reached over 300 individuals, and thousands of people kept the conversations going globally using #BlackInImmuno and #BlackInImmunoWeek on social media from five continents. Below, we highlight the events and significant takeaways of the week.

    View details for DOI 10.4049/jimmunol.2100667

    View details for PubMedID 34607907

  • Niche-directed therapy in acute myeloid leukemia: optimization of stem cell competition for niche occupancy. Leukemia & lymphoma Patel, S. A., Dalela, D., Fan, A. C., Lloyd, M. R., Zhang, T. Y. 2021: 1-9

    Abstract

    Acute myeloid leukemia (AML) is an aggressive malignancy of stem cell origin that contributes to significant morbidity and mortality. The long-term prognosis remains dismal given the high likelihood for primary refractory or relapsed disease. An essential component of relapse is resurgence from the bone marrow. To date, the murine hematopoietic stem cell (HSC) niche has been clearly defined, but the human HSC niche is less well understood. The design of niche-based targeted therapies for AML must account for which cellular subsets compete for stem cell occupancy within respective bone marrow microenvironments. In this review, we highlight the principles of stem cell niche biology and discuss translational insights into the AML microenvironment as of 2021. Optimization of competition for niche occupancy is important for the elimination of measurable residual disease (MRD). Some of these novel therapeutics are in the pharmacologic pipeline for AML and may be especially useful in the setting of MRD.

    View details for DOI 10.1080/10428194.2021.1966779

    View details for PubMedID 34407733

  • Reprogramming cancer into antigen presenting cells as a novel immunotherapy. Linde, M. H., Gurev, S. F., Phan, P., Zhao, F., Gars, E. J., Stafford, M., Kohnke, T., Marshall, P. L., Fan, A. C., Dove, C. G., Linde, I. L., Miller, L. P., Majzner, R. G., Zhang, T., Majeti, R. AMER ASSOC CANCER RESEARCH. 2021

    View details for Web of Science ID 000680263502148

  • NOT-Gated CD93 CAR T Cells Effectively Target AML with Minimized Endothelial Cross-Reactivity. Blood cancer discovery Richards, R. M., Zhao, F., Freitas, K. A., Parker, K. R., Xu, P., Fan, A., Sotillo, E., Daugaard, M., Oo, H. Z., Liu, J., Hong, W. J., Sorensen, P. H., Chang, H. Y., Satpathy, A. T., Majzner, R. G., Majeti, R., Mackall, C. L. 2021; 2 (6): 648-665

    Abstract

    Chimeric antigen receptor (CAR) T cells hold promise for the treatment of acute myeloid leukemia (AML), but optimal targets remain to be defined. We demonstrate that CD93 CAR T cells engineered from a novel humanized CD93-specific binder potently kill AML in vitro and in vivo but spare hematopoietic stem and progenitor cells (HSPC). No toxicity is seen in murine models, but CD93 is expressed on human endothelial cells, and CD93 CAR T cells recognize and kill endothelial cell lines. We identify other AML CAR T-cell targets with overlapping expression on endothelial cells, especially in the context of proinflammatory cytokines. To address the challenge of endothelial-specific cross-reactivity, we provide proof of concept for NOT-gated CD93 CAR T cells that circumvent endothelial cell toxicity in a relevant model system. We also identify candidates for combinatorial targeting by profiling the transcriptome of AML and endothelial cells at baseline and after exposure to proinflammatory cytokines.CD93 CAR T cells eliminate AML and spare HSPCs but exert on-target, off-tumor toxicity to endothelial cells. We show coexpression of other AML targets on endothelial cells, introduce a novel NOT-gated strategy to mitigate endothelial toxicity, and demonstrate use of high-dimensional transcriptomic profiling for rational design of combinatorial immunotherapies.See related commentary by Velasquez and Gottschalk, p. 559. This article is highlighted in the In This Issue feature, p. 549.

    View details for DOI 10.1158/2643-3230.BCD-20-0208

    View details for PubMedID 34778803

    View details for PubMedCentralID PMC8580619

  • IL-3 RESCUES PROLIFERATIVE DEFECTS IN INFLAMMATION-SENSITIVE RUNX1 DEFICIENT HUMAN HEMATOPOIETIC STEM AND PROGENITOR CELLS Fan, A., Azizi, A., Dutta, R., Nakauchi, Y., Nuno, K., Zhao, F., Reinisch, A., Majeti, R. ELSEVIER SCIENCE INC. 2020: S59

    View details for Web of Science ID 000655609700105

  • Azacitidine and Ascorbate Inhibit the Competitive Outgrowth of Human TET2 Mutant HSPCs in a Xenograft Model of Pre-Leukemia Nakauchi, Y., Thomas, D., Sharma, R., Corces, M., Reinisch, A., Cruz, D., Koehnke, T., Karigane, D., Fan, A., Majeti, R. AMER SOC HEMATOLOGY. 2018

    View details for DOI 10.1182/blood-2018-99-113907

    View details for Web of Science ID 000454837602264

  • scDual-Seq: mapping the gene regulatory program of Salmonella infection by host and pathogen single-cell RNA-sequencing GENOME BIOLOGY Avital, G., Avraham, R., Fan, A., Hashimshony, T., Hung, D. T., Yanai, I. 2017; 18: 200

    Abstract

    The interaction between a pathogen and a host is a highly dynamic process in which both agents activate complex programs. Here, we introduce a single-cell RNA-sequencing method, scDual-Seq, that simultaneously captures both host and pathogen transcriptomes. We use it to study the process of infection of individual mouse macrophages with the intracellular pathogen Salmonella typhimurium. Among the infected macrophages, we find three subpopulations and we show evidence for a linear progression through these subpopulations, supporting a model in which these three states correspond to consecutive stages of infection.

    View details for DOI 10.1186/s13059-017-1340-x

    View details for Web of Science ID 000413769600001

    View details for PubMedID 29073931

    View details for PubMedCentralID PMC5658913

  • A highly multiplexed and sensitive RNA-seq protocol for simultaneous analysis of host and pathogen transcriptomes. Nature protocols Avraham, R., Haseley, N., Fan, A., Bloom-Ackermann, Z., Livny, J., Hung, D. T. 2016; 11 (8): 1477-1491

    Abstract

    The ability to simultaneously characterize the bacterial and host expression programs during infection would facilitate a comprehensive understanding of pathogen-host interactions. Although RNA sequencing (RNA-seq) has greatly advanced our ability to study the transcriptomes of prokaryotes and eukaryotes separately, limitations in existing protocols for the generation and analysis of RNA-seq data have hindered simultaneous profiling of host and bacterial pathogen transcripts from the same sample. Here we provide a detailed protocol for simultaneous analysis of host and bacterial transcripts by RNA-seq. Importantly, this protocol details the steps required for efficient host and bacteria lysis, barcoding of samples, technical advances in sample preparation for low-yield sample inputs and a computational pipeline for analysis of both mammalian and microbial reads from mixed host-pathogen RNA-seq data. Sample preparation takes 3 d from cultured cells to pooled libraries. Data analysis takes an additional day. Compared with previous methods, the protocol detailed here provides a sensitive, facile and generalizable approach that is suitable for large-scale studies and will enable the field to obtain in-depth analysis of host-pathogen interactions in infection models.

    View details for DOI 10.1038/nprot.2016.090

    View details for PubMedID 27442864

https://orcid.org/0000-0003-1612-1862