OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 09/30/2024)

NAME: Allred, Jeremy

eRA COMMONS USER NAME (credential, e.g., agency login):  JALLRED

POSITION TITLE: Assistant Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

A.        Personal Statement
My long-term career goal as a physician-scientist, with my feet firmly planted in both the clinic and research worlds, is to provide exceptional treatment to patients with hematologic malignancy. My focus will be on innovations in bone marrow transplantation and cellular therapy with curative intent for patients with complex and refractory diseases. A primary driver of innovation in oncologic care has been strong investigational research into the fundamental biology of cancer and its complex relationship with a patient’s immune system. Recent innovations in the fields of cellular therapy and immunotherapy have begun to fundamentally change how we practice oncology. My primary research interests and record are reflective of these advances and of my clinical interests, namely elucidating key biological mechanisms of immune targeting and tolerance and leveraging this knowledge to design novel anti-cancer therapies for my patients. A primary focus of my current research is developing new T cell therapies to treat blood cancers. In recent years, engineered T cells with chimeric antigen receptors have revolutionized treatment of certain types of chemotherapy refractory leukemias and lymphomas. While the efficacy of these first-generation therapies has been nothing short of astounding, significant challenges remain including delays in manufacturing time, unique and sometimes fatal toxicities, heterogeneity in product efficacy between patients, and excessive cost. All of these challenges limit the promise of this unique technology. My overarching goal is to leverage my skills as a basic scientist and clinician and to foster cross disciplinary collaborations to bring the next generation of cellular therapies to patients with cancer. I collaborate closely with my scientific mentor Dr. Bruce Blazar on this work and have recently teamed up with Dr. Joseph Muretta and Dr. Wendy Gordon, MPIs of the current proposal, to develop a soluble Notch activator that, if successful, would transform our ability to address next-generation T cell engineering challenges and provide a path toward cost-effective iPSC-based T cells for cellular therapies.

B.        Positions, Scientific Appointments, and Honors
2002 – 2005                Undergraduate Researcher –Verfaille Laboratory, University of Minnesota

2006 – 2007                Researcher – Lee Laboratory, University of Minnesota

2007 – 2010                Researcher – Kaufman Laboratory, University of Minnesota

2011 – 2011                NHLBI T-35 Summer Research Program – Rao Laboratory, Blood Center of Wisconsin

2012 – 2013                HHMI Medical Research Fellow – Orkin Laboratory, Dana Farber Cancer Institute

2015 – 2021                Physician Scientist Training Program, University of Minnesota

2018 – 2021                NIH T32 Training grant program, University of Minnesota

2018 – 2021                Post-doctoral fellowship - Blazar Laboratory, University of Minnesota

2021 –                                     Instructor – Division of Hematology, Oncology and Transplantation, U of Minnesota

Other Experience and Professional Memberships

2017 –                                     Member, American Society of Hematology

2017 –                                     Member, American Society of Clinical Oncology      

2018 –                                     Member, American Society of Gene & Cell Therapy

2018 –                                     Member, American Society of Transplantation and Cellular Therapy

2018 –                                     Member, American Association of Immunologists

Honors and Awards

2013                                        Scholarship, Edmund J and Estelle D. Walker, Medical College of Wisconsin

2012                                        HHMI Medical Research Fellowship award, Boston MA

2015                                        Honors in Research, Medical College of Wisconsin

2019                                        Academic Investment Education Program Research award, U of Minnesota

2021                                        ASH Research Training Award for Fellows, University of Minnesota

2021                                        NIH Loan Repayment Program, University of Minnesota

C.        Contributions to Science
 

1. Early Career: My early career research focused primarily on projects revolving around using human pluripotent stem cells with the goals of both modelling and developing novel therapies to human disease. Shortly after graduating college, I joined Dr. Dan Kaufman’s lab were I was an integral member of the researcher team culturing, expanding, and genetically modifying human embryonic stem cells that were used to study the generation of various cell types, including osteoclasts, hematopoietic progenitors, and natural killer (NK) cells, a type of lymphocyte with potent anti-cancer properties. Specifically, I designed, cloned constructs, and generated novel human embryonic stem cell (hESC) lines with reporter systems that helped elucidate pathways of cellular commitment during NK differentiation and developed novel protocols for generating osteoclasts from hESC derived hematopoietic progenitors.
   1. Ni Z, Knorr DA, Bendzick L, Allred J, Kaufman DS; “Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo,” Stem Cells (2013 Dec 4. doi: 10.1002/stem.1611)
   2. Hill KL, Obrtikova P, Alvarez DF, King JA, Keirstead SA, Allred JR, Kaufman DS; “Human embryonic stem cell-derived vascular progenitor cells capable of endothelial and smooth muscle cell function,” Experimental Hematology (2010 Mar; 38-3:246-257)
   3. Islam MS, Allred JR, Hill KL, Hexum MK, Kaufman DS; “Osteoclasts from human embryonic stem cell-derived hematopoietic progenitors support development of an in vitro niche Microenvironment,” Poster Abstract, accepted American Society of Hematology Annual Meeting (2009)

2. Graduate Career: My research efforts during medical school focused on elucidating mechanisms of malignant transformation of blood progenitors into leukemia. My research specifically focused on the transcription factor Sal4, a critical player in the stem cell self-renewal program. Additionally, I made significant contributions to projects outlining the role of epigenetic modulation of enhancer transcribed RNAs. My research experience during medical school inspired me to apply for support for a year-long research project in the lab of Dr. Orkin as a part of the HHMI Medical Research fellows program using induced pluripotent stem cells derived from children with Downs syndrome as a model system for studying the role of Trisomy 21 in abnormal B cell development and risk of B-ALL. This work, based on a project I proposed, led to a publication in 2018.

1. Milanovich S, Peterson J, Allred J, Stelloh C, Fisher J, Duncan S, Rao S; “Sall4 regulates normal and malignant hematopoiesis in a dose dependent manner,” Experimental Hematology (2015 Jan;43(1):53-64.e1-8)
2. Pulakanti K, Pinello L, Stelloh C, Blinka S, Allred J, Milanovich S, Kiblawi S, Peterson J, Wang A, Yuan GC, Rao S; “Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions,” Epigenetics (2013 Dec 1;8(12):1303-20)
3. Allred JA, Stelloh C, Milanovich S, Rao S; “Identifying a leukemia stem cell specific self-renewal program,” Poster Abstract, MCW Medical Student Summer Research Program (2011)
4. MacLean GA, McEldoon J, Huang J, Allred J, Canver MC, Orkin SH; “Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoeisis in Trisomy 21 Pluripotent Stem Cells,” Science Reports (2018 May 22; 8(1);8001

3. Postdoctoral Career: During the post-doctoral research portion of my Hematology/Oncology fellowship, I joined the lab of Dr. Bruce Blazar with the support of a competitively awarded NIH T32 grant. My research explores lymphocyte development from human pluripotent stem cells as a novel source of T cells for use in cellular therapies such as CAR-T for patients with hematologic malignancies. The goal of my work is to develop induced pluripotent stem cell technology into a viable alternative source of highly active T lymphocytes for cellular therapy. Additionally, I pursued training in clinical malignant hematology, bone marrow transplantation, and cellular therapy and recently joined the faculty at the Instructor level. My objective is to publish in high-impact journals and leverage this work toward NIH K-series grants with the goal of being an independently funded physician-scientist.
   1. Allred JR*, Williams RL*, Blazar BR (*equal contributors). Comparing iPSCs and adult stem cells for T cell generation. Induced Pluripotent Stem Cells – Novel Concepts. Elsevier series "Advances in Stem Cell Biology" Elsevier (pub), 2020 (Accepted)
   2. Allred J, Bharucha K, Ozutemiz C, He F, Janakiram M, Maakaron J, Carrier C, Grzywacz, Bachanova V; “Chimeric antigen receptor T-cell therapy for HIV-associated diffuse large B-cell Lymphoma: case report and management recommendations.” Bone Marrow Transplantation (2020 Aug 6; 2020)
   3. Goyal A, Allred J, Kandaswamy R, Finger E, Keys D, Riad S, Holtan S; “Solid-organ transplant lymphocyte engraftment and GVHD resolved by high-dose ATG.” Bone Marrow Transplantation (2021, in review)
   4. Wilkey, A, Allred J; “Chemotherapy.” Perioperative Manual Coexisting Diseases (2020, in review)