University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Francis C. Szoka, Jr., PhD

Francis C. Szoka, Jr., PhD

Professor, Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, UCSF

Cancer Center Program Memberships

Experimental Therapeutics

Research Summary

My group has focused on improving delivery of drugs into solid tumors. We have extensively investigated ways using polymers, proteins, and nanocarriers to overcome barriers that impede drug distribution into solid tumors including: improving carrier circulation half-life, optimizing drug release, enhancing extravasation, disrupting interstitial tumor matrix, and improving convective fluid movements within a tumor. Although we have made progress to deliver drugs into solid tumors, the barriers still stand.

My lab uses macrophages to transport therapeutic agents into defined inflammatory lesions, such as solid tumors, or into fungal or tuberculosis lesions. Our approach is to manufacture macrophage precursor cells that can be rapidly expanded, differentiated into macrophages, and engineered to deliver therapeutic agents throughout the tumor matrix or nidus of infection. To translate this idea into a useful medicine requires a more detailed knowledge of how to create a transplantable macrophage that can be quickly generated in high numbers, as well as how to modify the macrophage with nanocarriers or genetic manipulations so it can deliver therapeutics in a controllable and predictable manner. We are encouraged that the macrophage approaches devised in our research might not only be used to treat cancer but also to treat a variety of other disorders including traumatic tissue injury and chronic inflammation.

Education

John Hopkins University, Baltimore, MD, A.B., 1965, Liberal Arts
University of Maryland, College Park, MD, M.S., 1971, Microbiology
SUNY/Buffalo, Buffalo, NY, Ph.D., 1976, Biochemistry


Professional Experience

  • 1969-1971
    Captain, U.S. Army; Director, Clinical Chemistry, Walson Army Hospital
  • 1976-1978
    NIH postdoctoral fellow, Dr. D. Papahadjopoulos, RPMI, Buffalo
  • 1978-1979
    Cancer Research Scientist, Roswell Park Cancer Institute, Buffalo
  • 1979-1980
    Assistant Professor of Physiology, Tufts Medical School
  • 1980-1985
    Assistant Professor of Pharmacy & Pharmaceutical Chemistry, University of California
  • 1985-1991
    Associate Professor of Pharmacy & Pharmaceutical Chemistry, University of California
  • 1991-present
    Professor of Biopharmaceutics & Pharmaceutical Chemistry, University of California

Selected Publications

  1. Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White PJ, McGarrah RW, Ilkayeva OR, Deleye Y, Oguri Y, Kuroda M, Ikeda K, Li H, Ueno A, Ohishi M, Ishikawa T, Kim K, Chen Y, Sponton CH, Pradhan RN, Majd H, Greiner VJ, Yoneshiro M, Brown Z, Chondronikola M, Takahashi H, Goto T, Kawada T, Sidossis L, Szoka FC, McManus MT, Saito M, Soga T, Kajimura S. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature. 2019 Aug; 572(7771):614-619.
    View on PubMed
  2. Dolor A, Sampson SL, Lazar AA, Lotz JC, Szoka FC, Fields AJ. Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition. PLoS One. 2019; 14(4):e0215218.
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  3. Tang J, Srinivasan S, Yuan W, Ming R, Liu Y, Dai Z, Noble CO, Hayes ME, Zheng N, Jiang W, Szoka FC, Schwendeman A. Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome. Eur J Pharm Biopharm. 2019 Jan; 134:107-116.
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  4. Dolor A, Kierstead P, Dai Z, Szoka FC. Correction: Sterol-modified PEG lipids: alteration of the bilayer anchoring moiety has an unexpected effect on liposome circulation. Chem Commun (Camb). 2018 11 13; 54(91):12891.
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  5. Dolor A, Kierstead P, Dai Z, Szoka FC. Sterol-modified PEG lipids: alteration of the bilayer anchoring moiety has an unexpected effect on liposome circulation. Chem Commun (Camb). 2018 Oct 28; 54(84):11949-11952.
    View on PubMed
  6. Dolor A, Szoka FC. Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery. Mol Pharm. 2018 06 04; 15(6):2069-2083.
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  7. Shaghaghi M, Keyvanloo A, Huang Z, Szoka FC, Thewalt JL. Constrained Versus Free Cholesterol in DPPC Membranes: A Comparison of Chain Ordering Ability Using Deuterium NMR. Langmuir. 2017 12 19; 33(50):14405-14413.
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  8. Lee S, Kivimäe S, Szoka FC. Clodronate Improves Survival of Transplanted Hoxb8 Myeloid Progenitors with Constitutively Active GMCSFR in Immunocompetent Mice. Mol Ther Methods Clin Dev. 2017 Dec 15; 7:60-73.
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  9. Iman M, Huang Z, Alavizadeh SH, Szoka FC, Jaafari MR. Biodistribution and In Vivo Antileishmanial Activity of 1,2-Distigmasterylhemisuccinoyl-sn-Glycero-3-Phosphocholine Liposome-Intercalated Amphotericin B. Antimicrob Agents Chemother. 2017 09; 61(9).
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  10. Kieler-Ferguson HM, Chan D, Sockolosky J, Finney L, Maxey E, Vogt S, Szoka FC. Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids. Eur J Pharm Sci. 2017 May 30; 103:85-93.
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  11. Tiffany M, Szoka FC. Co-localization of fluorescent labeled lipid nanoparticles with specifically tagged subcellular compartments by single particle tracking at low nanoparticle to cell ratios. J Drug Target. 2016 11; 24(9):857-864.
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  12. Yuan W, Kuai R, Dai Z, Yuan Y, Zheng N, Jiang W, Noble C, Hayes M, Szoka FC, Schwendeman A. Development of a Flow-Through USP-4 Apparatus Drug Release Assay to Evaluate Doxorubicin Liposomes. AAPS J. 2017 01; 19(1):150-160.
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  13. Lee S, Kivimäe S, Dolor A, Szoka FC. Macrophage-based cell therapies: The long and winding road. J Control Release. 2016 10 28; 240:527-540.
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  14. Kierstead PH, Okochi H, Venditto VJ, Chuong TC, Kivimae S, Fréchet JMJ, Szoka FC. The effect of polymer backbone chemistry on the induction of the accelerated blood clearance in polymer modified liposomes. J Control Release. 2015 Sep 10; 213:1-9.
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  15. Sockolosky JT, Szoka FC. The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy. Adv Drug Deliv Rev. 2015 Aug 30; 91:109-24.
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  16. Venditto VJ, Dolor A, Kohli A, Salentinig S, Boyd BJ, Szoka FC. Sulfated quaternary amine lipids: a new class of inverse charge zwitterlipids. Chem Commun (Camb). 2014 Aug 21; 50(65):9109-11.
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  17. Sockolosky JT, Kivimäe S, Szoka FC. Fusion of a short peptide that binds immunoglobulin G to a recombinant protein substantially increases its plasma half-life in mice. PLoS One. 2014; 9(7):e102566.
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  18. Venditto VJ, Wieczorek L, Molnar S, Teque F, Landucci G, Watson DS, Forthal D, Polonis VR, Levy JA, Szoka FC. Chemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies in rabbits. Clin Vaccine Immunol. 2014 Aug; 21(8):1086-93.
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  19. Kohli AG, Kivimäe S, Tiffany MR, Szoka FC. Improving the distribution of Doxil® in the tumor matrix by depletion of tumor hyaluronan. J Control Release. 2014 Oct 10; 191:105-14.
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  20. Kohli AG, Kierstead PH, Venditto VJ, Walsh CL, Szoka FC. Designer lipids for drug delivery: from heads to tails. J Control Release. 2014 Sep 28; 190:274-87.
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