Research Summary

As a physician-scientist and member of the Hematological Malignancies and Stem Cell Transplantation Program and Helen Diller Family Cancer Center at UCSF, my clinical focus has been the treatment of hematological malignancies, combining chemotherapeutic and autologous or allogeneic bone marrow/ stem cell transplantation approaches. My laboratory has focused on the development of gene transfer and stem cell transplantation approaches for the treatment of hematologic disorders, with a current focus on the development of immunotherapeutic approaches to treat minimal residual disease (MRD) in older patients with acute myelogenous leukemia (AML). There is a major clinical unmet need for effective and safe therapies to increase progression-free and overall survival in older individuals with leukemia whose prognosis is grim.
Compelling evidence for the efficacy of immunotherapy in eliminating minimal residual disease (MRD) is provided by the superior outcomes of allogeneic hematopoietic stem cell transplants (HSCT) due to graft vs leukemia (GVL) effects. However, patients > 60 yo are often ineligible for allo-HSCT. Two vaccine approaches are being developed as part of a collaborative consortium at UCSF, UCLA, UC Davis, and King’s College, London.
Our vaccine project focuses on genetic engineering of autologous whole cell AML vaccines to express CD80, and IL-15, and IL-15 Receptor alpha (IL-15Rα). The leukemia-specific cytolytic activity stimulated by engineered, irradiated AML cell vaccines expressing IL-15/IL-15Ra/CD80 was tested in the murine 32Dp210 myeloid leukemia model that recapitulates many features of human AML. Proof of concept (POC) studies showed that treatment of leukemia-bearing hosts induced superior anti-leukemic immunity when compared with vaccines expressing either CD80, or IL15-IL15Rα alone and eradicated leukemia 80% in leukemic mice an effect mediated by CD8+ T cells. (Shi, Y. et al (2018)).
Based on these proof of concept studies we received a Catalyst award through the CTSI at UCSF, a Translational Research Program grant from the Leukemia and Lymphoma Society in 2017, and a CIRM Translational-1 grant in 2018 to pursue non-overlapping studies with cGMP reagents supporting submission of a Pre-IND package to the FDA. Most recently, we were awarded a CIRM CLIN 1 grant (12/2022)to pursue IND enabling studies. These studies are being pursued as part of a collaborative consortium with investigators at UCSF (M. Rosenblum, L. Damon, A. Nambiar, A.Combes and K. Ganapathi), UCLA (Donald Kohn), and King's College London (Farzin Farzaneh).

Research Funding

  • February 1, 2018 - January 31, 2023 - Developing Engineered Autologous Leukemia vaccines to Target Residual Leukemic Stem Cells , PI . Sponsor: CIRM TRAN-1, Sponsor Award ID:
  • October 1, 2017 - September 30, 2022 - Inducing effective anti-leukemic immunity with novel AML vaccines expressing IL15/IL-15Ra/CD80 , PI . Sponsor: Leukemia Lymphoma Society, Sponsor Award ID:
  • December 1, 2011 - November 30, 2015 - Lentivirus-based positive/negative selection in minimally ablative transplants , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL107974
  • August 6, 2013 - July 31, 2015 - Efficacy and safety of novel CD80 IL15 IL15Ra expressing autologous AML vaccines , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA177284
  • May 12, 2008 - April 30, 2013 - Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary Disorders , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL082665
  • April 15, 2006 - April 14, 2012 - Tolerance Induction by Neonatal Gene Delivery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK072537
  • September 20, 2005 - August 31, 2008 - In Vivo Stem Cell Selection in Neonatal Allo-Transplants , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21DK069430
  • September 30, 1994 - August 31, 2007 - GENE THERAPY STRATEGIES FOR SICKLE CELL DISEASE , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01HL053762
  • September 1, 1999 - August 31, 2004 - SEQUENTIAL PRE AND POSTNATAL GENE THERAPY OF HEMOPHILIA , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HL062389
  • April 1, 1978 - March 31, 2004 - NORTHERN CALIFORNIA COMPREHENSIVE SICKLE CELL CENTER , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P60HL020985
  • March 1, 1992 - July 31, 1997 - ANALYSIS OF B GLOBIN LOCUS REGULATION BY YAC TRANSFER , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K11HL002711

Education

Swarthmore College, Swarthmore, PA, B.A., 1977, Biology
Harvard Medical School, M.D., 1981, Medicine
Univ of California, San Francisco, CA, Resident, 1981-84, Internal Medicine
Univ of California, San Francisco, CA, Fellow, 1984-87, Hematology/Oncology

Honors & Awards

  • 1988-1990
    American Cancer Society Fellowship
  • 1991-1992
    Howard Hughes Medical Institute Fellowship
  • 1992-1997
    NIH Physician Scientist Award

Selected Publications

  1. Othman T, Lo MM, Andreadis CB, Damon LE, Ferng TT, Gaensler KML, Lee JC, Martin TG, Olin RL, Sayre PH, Smith CC, Logan AC. Single-center experience with nelarabine, etoposide, and cyclophosphamide in adults with relapsed/refractory T-acute lymphoblastic leukemia/lymphoma. Leuk Lymphoma. 2025 May 07; 1-4.  View on PubMed
  2. Greenberg PL, Stone RM, Abaza Y, Al-Kali A, Anand S, Ball B, Bennett JM, Borate U, Brunner AM, Chai-Ho W, Curtin P, DeZern AE, Gaensler K, Gahvari Z, Garcia-Manero G, Griffiths EA, Haque T, Jacoby M, Jonas BA, Keel S, Khanal R, Kishtagari A, Madanat Y, Maness LJ, McCurdy SR, McMahon C, Odenike O, Osman A, Reddy VV, Sallman DA, Sayar H, Shallis R, Singh A, Tanaka T, Thota S, Kovach E, Nguyen J, Hochstetler C NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 2.2025.  View on PubMed
  3. Huang LW, Shi Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Boscardin WJ, Steinman MA, Olin RL. Association of geriatric measures and global frailty with cognitive decline after allogeneic hematopoietic cell transplantation in older adults. J Geriatr Oncol. 2023 11; 14(8):101623.  View on PubMed
  4. Huang LW, Sheng Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Huang CY, Olin RL. Patterns and Predictors of Functional Decline after Allogeneic Hematopoietic Cell Transplantation in Older Adults. Transplant Cell Ther. 2022 06; 28(6):309.e1-309.e9.  View on PubMed
  5. Greenberg PL, Stone RM, Al-Kali A, Bennett JM, Borate U, Brunner AM, Chai-Ho W, Curtin P, de Castro CM, Deeg HJ, DeZern AE, Dinner S, Foucar C, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Jonas BA, Keel S, Madanat Y, Maness LJ, Mangan J, McCurdy S, McMahon C, Patel B, Reddy VV, Sallman DA, Shallis R, Shami PJ, Thota S, Varshavsky-Yanovsky AN, Westervelt P, Hollinger E, Shead DA, Hochstetler C NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 3.2022.  View on PubMed
  6. Wang VE, Blaser BW, Patel RK, Behbehani GK, Rao AA, Durbin-Johnson B, Jiang T, Logan AC, Settles M, Mannis GN, Olin R, Damon LE, Martin TG, Sayre PH, Gaensler KM, McMahon E, Flanders M, Weinberg V, Ye CJ, Carbone DP, Munster PN, Fragiadakis GK, McCormick F, Andreadis C. Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. Blood Cancer Discov. 2021 09; 2(5):434-449.  View on PubMed
  7. Huang LW, Sheng Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Steinman MA, Huang CY, Olin RL. Functional Status as Measured by Geriatric Assessment Predicts Inferior Survival in Older Allogeneic Hematopoietic Cell Transplantation Recipients. Biol Blood Marrow Transplant. 2020 01; 26(1):189-196.  View on PubMed
  8. Wieduwilt MJ, Pawlowska N, Thomas S, Olin R, Logan AC, Damon LE, Martin T, Kang M, Sayre PH, Boyer W, Gaensler KML, Anderson K, Munster PN, Andreadis C. Histone Deacetylase Inhibition with Panobinostat Combined with Intensive Induction Chemotherapy in Older Patients with Acute Myeloid Leukemia: Phase I Study Results. Clin Cancer Res. 2019 08 15; 25(16):4917-4923.  View on PubMed
  9. Shi Y, Dincheva-Vogel L, Ayemoba CE, Fung JP, Bergamaschi C, Pavlakis GN, Farzaneh F, Gaensler KML. IL-15/IL-15Rα/CD80-expressing AML cell vaccines eradicate minimal residual disease in leukemic mice. Blood Adv. 2018 11 27; 2(22):3177-3192.  View on PubMed
  10. Saeed L, Schmidt TH, Gensler LS, Gross AJ, Fox LP, Scharschmidt TC, Gaensler K, Naik H, Rosenblum MA, Shinkai K Successful treatment of mucous membrane pemphigoid with bortezomib.  View on PubMed
  11. Greenberg PL, Stone RM, Al-Kali A, Barta SK, Bejar R, Bennett JM, Carraway H, De Castro CM, Deeg HJ, DeZern AE, Fathi AT, Frankfurt O, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Horsfall R, Johnson RA, Juckett M, Klimek VM, Komrokji R, Kujawski LA, Maness LJ, O'Donnell MR, Pollyea DA, Shami PJ, Stein BL, Walker AR, Westervelt P, Zeidan A, Shead DA, Smith C. Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017 01; 15(1):60-87.  View on PubMed
  12. Mannis GN, Martin TG, Damon LE, Andreadis C, Olin RL, Kong KA, Faham M, Hwang J, Ai WZ, Gaensler KML, Sayre PH, Wolf JL, Logan AC. Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016 06; 22(6):1030-1036.  View on PubMed
  13. Mannis GN, Martin TG, Damon LE, Logan AC, Olin RL, Flanders MD, Ai WZ, Gaensler KM, Kaplan LD, Sayre PH, Smith CC, Wolf JL, Andreadis C. Long-term outcomes of patients with intermediate-risk acute myeloid leukemia treated with autologous hematopoietic cell transplant in first complete remission. Leuk Lymphoma. 2016 07; 57(7):1560-6.  View on PubMed
  14. Ikuta T, Sellak H, Odo N, Adekile AD, Gaensler KM. Nitric Oxide-cGMP Signaling Stimulates Erythropoiesis through Multiple Lineage-Specific Transcription Factors: Clinical Implications and a Novel Target for Erythropoiesis. PLoS One. 2016; 11(1):e0144561.  View on PubMed
  15. Li B, Luo X, Deng B, Wang J, McComb DW, Shi Y, Gaensler KM, Tan X, Dunn AL, Kerlin BA, Dong Y. An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo. Nano Lett. 2015 Dec 09; 15(12):8099-107.  View on PubMed
  16. Tye GJ, Ioannou K, Amofah E, Quartey-Papafio R, Westrop SJ, Krishnamurthy P, Noble A, Harrison PM, Gaensler KML, Barber LD, Farzaneh F. The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumor-associated self-antigen in aged, immunosenescent mice. Immun Ageing. 2015; 12:6.  View on PubMed
  17. Greenberg PL, Stone RM, Bejar R, Bennett JM, Bloomfield CD, Borate U, De Castro CM, Deeg HJ, DeZern AE, Fathi AT, Frankfurt O, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Klimek V, Komrokji R, Kujawski LA, Maness LJ, O'Donnell MR, Pollyea DA, Scott B, Shami PJ, Stein BL, Westervelt P, Wheeler B, Shead DA, Smith C, National comprehensive cancer network. Myelodysplastic syndromes, version 2.2015. J Natl Compr Canc Netw. 2015 Mar; 13(3):261-72.  View on PubMed
  18. Mannis GN, Andreadis C, Logan AC, Damon LE, Benet LZ, Ai WZ, Gaensler KM, Kaplan LD, Koplowicz YB, Linker CA, Olin RL, Sayre PH, Smith CC, Sudhindra A, Venstrom JM, Wolf JL, Martin TG. A phase I study of targeted, dose-escalated intravenous busulfan in combination with etoposide as myeloablative therapy for autologous stem cell transplantation in acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2015 Jun; 15(6):377-83.  View on PubMed
  19. Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector LP, Porteus MH, Gaensler KM, Kay MA. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature. 2015 Jan 15; 517(7534):360-4.  View on PubMed
  20. Park I, Mukherjee J, Ito M, Chaumeil MM, Jalbert LE, Gaensler K, Ronen SM, Nelson SJ, Pieper RO. Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells. Cancer Res. 2014 Dec 01; 74(23):7115-24.  View on PubMed

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