Kendall Smith

Last updated March 09, 2024

Kendall A. Smith is an American scientist most well-known for his work on interleukins, the regulatory molecules of the immune system, which has led to many of the new present-day therapies for immunological disorders, transplant rejection, infectious diseases and cancer.^[1]^[2] Smith is a Professor Emeritus of Medicine at Weill Cornell Medicine.^[3]

Early life

Kendall Arthur Smith was born in Akron, Ohio, where he grew up as the second child of Robert Lyman Smith and Juanita Murphy Smith. He attended Fairlawn Primary School, Simon Perkins Junior High School followed by Buchtel High School in Akron, graduating in 1960.

Medical and scientific training

Smith graduated from Denison University, Granville, Ohio with a B.S. in biology (1964).^[4] He graduated summa cum laude from the Ohio State University College of Medicine in 1968, then trained in Internal Medicine at Yale-New Haven Hospital (1968-1970). Smith then trained at the National Cancer Institute, Dartmouth Medical School and L’Institut de Cancerologie et d’Immunogenetique in Villejuif, France (1970-’74).

Career

Smith joined the faculty of Dartmouth Medical School (Hanover, N.H.) as an Assistant Professor of Medicine in Hematology & Oncology in 1974, progressing to Associate Professor (1978) and Professor (1982). At the school, Smith focused his research on the immune system. By the 1970s, it had become clear that white blood cells are responsible for immune responses, but how these responses are initiated and regulated was not yet understood. The first molecularly defined T cell cytokine, interleukin-2 (IL-2), was originally described by Smith.^[5] His findings had a significant impact on immunology research and paved the way for the discovery of numerous humoral mediators of cell-mediated immunity.^[6] In groundbreaking research, Smith led a team that employed meticulous protein enrichment methods to purify TCGF (IL-2) to a state of purity and produce bioactive, biosynthetically radiolabeled TCGF. The introduction of radiolabeled TCGF/IL-2 allowed for an examination of its interaction with T cells, leading to a pivotal finding: the biological impacts of TCGF were facilitated by a high-affinity cytokine receptor that was selectively expressed on T cells activated through their T cell antigen receptor, thus underscoring the immune specificity of IL-2's effects.^[6]

In 1993, Smith moved to Weill Cornell Medicine in New York City to conduct clinical research in AIDS. There he served as the Chief of The Division of Immunology as well as the Co-Chair of the Immunology Program of The Graduate School of Biomedical Sciences, a joint program between Cornell and Sloan-Kettering Institute. He also served as the Director of The Tr-Institutional MD/PhD Program, a joint effort between Cornell, Sloan-Kettering and the Rockefeller University. Having extended his research to the clinic, by 1999, Smith established that low, physiological doses of interleukins could stimulate immune responses without toxicity.^[7]^[8]

In 1993 Smith moved to Weill Cornell Medicine in New York City to conduct clinical research in AIDS. There he served as the Chief of The Division of Immunology as well as the Co-Chair of the Immunology Program of The Graduate School of Biomedical Sciences, a joint program between Cornell and Sloan-Kettering Institute. He also served as the Director of The Tr-Institutional MD/PhD Program, a joint effort between Cornell, Sloan-Kettering and the Rockefeller University.

Publications

Interleukin 2. Academic Press, Inc. 1988. ISBN 9780126514209.
The Quantal Theory of Immunity: The Molecular Basis of Autoimmunity and Leukemia. World Scientific Publishing Co. Pte. Ltd. 2010. ISBN 9789814271752.
Molecular Immunity: A Chronology of 60 Years of Discovery. World Scientific Publishing Co. Pte. Ltd. 2019. ISBN 9789813231702.
The Interleukin Revolution. The Troy Bookmakers. 2023. ISBN 9781614687986.

Honors and awards

1965 Nu Sigma Nu Award for the Outstanding First year Medical Student
1966 The Chauncy Leake Award
1967 Alpha Omega Alpha honor society
1968 Landacre Society – Student Research Honorary Society, President
1968 Robert Nelson Watman Award for Outstanding Achievement in Research and Medicine
1968 M.D. summa cum laude
1979 Elected as Fellow to the American College of Physicians
1981 Elected to the American Society for Clinical Investigation
1989 Friedrich-Sasse Foundation Award
1993 Denison University Alumni Citation Award
2009 Alumni Achievement Award, The Ohio State University College of Medicine

Journal articles

The Long-Term Culture of Antigen-Specific T Cytotoxic T cells. Nature, 268:154-156, 1977.
T Cell Growth Factor: Parameters of Production and a Quantitative Microassay for Activity. J. Immunol, 120:2027-32, 1978.
The Functional Relationship of the Interleukins. J. Exp. Med. 151:1551-56, 1980.
The Biochemical Characterization of the IL2 Molecule. Mol. Immunol. 18:1087-94, 1981.
T Cell Growth Factor Receptors: Quantitation, Specificity and Biological Relevance. J. Exp. Med. 154: 1455-74, 1981.
Production and Characterization of Monoclonal Antibodies to Interleukin 2: Strategies and Tactics. J. Immunol 131: 1808-15. 1983.
The Interleukin T cell System: A New Cell Growth Model. Science. 224: 1312-16, 1984.
The Interleukin 2 Receptor: Functional Consequences of it’s Bimolecular Structure. J. Exp. Med. 166: 1055-69. 1987.
Differentiation of T Cell Lymphokine Gene Expression: The in vitro Generation of T Cell Memory. J. Exp. Med. 173:25-36. 1991.
Isolation of Interleukin2-induced Immediate-Early Genes. PNAS. 90:2719-23. 1993.
Rational Interleukin 2 Therapy for HIV-Positive Individuals: Daily Low Doses Enhance Immune Function Without Toxicity. PNAS. 93:10405-10, 1996.
Therapeutic Use of IL2 to Enhance Antiviral T Cell Responses in vivo. Nature Med. 9:1-8, 2003.
PD1 Combination Therapy with IL2 Modifies CD8+ T Cell Exhaustion. Nature. 610:173-81, 2022.

Related Research Articles

Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.

Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively.

<span class="mw-page-title-main">Weill Cornell Graduate School of Medical Sciences</span> Graduate college for biomedical sciences located in New York City

The Weill Cornell Graduate School of Medical Sciences (WCGS), formerly known as the Cornell University Graduate School of Medical Sciences, is a graduate college of Cornell University that was founded in 1952 as an academic partnership between two major medical institutions in New York City: the Weill Cornell Medical College and the Sloan Kettering Institute. Cornell is involved in the Tri-Institutional MD-PhD Program with Rockefeller University and the Sloan Kettering Institute; each of these three institutions is part of a large biomedical center extending along York Avenue between 65th and 72nd Streets on the Upper East Side of Manhattan.

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

Interleukin 7 (IL-7) is a protein that in humans is encoded by the IL7 gene.

<span class="mw-page-title-main">Interleukin 1 beta</span> Mammalian protein found in Homo sapiens

Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the IL1B gene. There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.

Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21, is a protein that in humans is encoded by the CR2 gene.

The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain or with IL-13Rα1.

Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene.

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.

<span class="mw-page-title-main">Avery August</span> Belizean-born American scientist (born 1964)

Avery August is a Belizean-born American scientist who is currently a professor of immunology and vice provost at Cornell University.

Joel N. Blankson is a professor at the Johns Hopkins School of Medicine in the Department of Medicine, Division of Infectious Diseases. Blankson is an expert on HIV infection, particularly HIV latency and long-term control of HIV infection. He is a lead investigator in studies on these topics and is frequently interviewed in the scientific and popular press. Blankson also practices internal and infectious diseases medicine in Lutherville, Maryland.

Sérgio A. Lira, is a Brazilian-born American immunologist who pioneered the use of genetic approaches to study the function of chemokines. His early studies were the first to show that chemokines played a major role on leukocyte trafficking to the brain, the lung and the thymus.

Paola Ricciardi-Castagnoli, is an Italian Immunologist based in Siena, Italy. Paola is the scientific director of Toscana Life Sciences Foundation (TLS) in Siena. She was former scientific director of the Singapore Immunology Network (SIgN).

James Patrick Allison is an American immunologist and Nobel laureate who holds the position of professor and chair of immunology and executive director of immunotherapy platform at the MD Anderson Cancer Center at the University of Texas.

Martin Turner is a molecular biologist and Immunologist and Head of the Immunology Programme at the Babraham Institute. His work has helped identify key molecular processes involved in the development of the immune system and its response to pathogens. His work has included research the fundamental mechanisms regulating gene expression by cells of the immune system.

Marcel R.M. van den Brink is a Dutch oncologist and researcher known for his research in hematopoietic stem cell transplantation for cancer patients.

Gene Martin Shearer is an American immunologist who works at the National Institutes of Health (NIH). He first achieved fame for his discovery in 1974 that T lymphocytes recognized chemically modified surface antigens only in the context of self major histocompatibility complex (MHC) encoded molecules, identifying the central feature of antigen recognition by T lymphocytes known as MHC restriction. His discovery of MHC restriction using chemically modified surface antigens was simultaneous with the discovery of MHC restricted T lymphocyte recognition of virus infected cells by Rolf Zinkernagel and Peter Doherty, who received the 1996 Nobel Prize in Physiology or Medicine.

Alexander Rudensky is an immunologist at Memorial Sloan Kettering Cancer Center known for his research on regulatory T cells and the transcription factor Foxp3.

David A. Scheinberg is an American physician, scientist, drug developer, and entrepreneur, who is currently Vincent Astor Chair, and Chairman of the Molecular Pharmacology Program at Memorial Sloan Kettering Cancer Center (MSK). He is a pioneer and inventor of targeted alpha particle therapies and alpha particle generators for use in patients with cancer.

References

↑ Smith, Kendall A (2017-09-06). Molecular Immunity. WORLD SCIENTIFIC. doi:10.1142/10755. ISBN 978-981-323-170-2.
↑ "Loop | Kendall Arthur Smith". loop.frontiersin.org. Retrieved 2021-06-02.
↑ "Faculty | Weill Department of Medicine". medicine.weill.cornell.edu. Retrieved 2021-06-02.
↑ University, Denison. "Kendall A. Smith". Denison University Alumni. Retrieved 2021-06-02.
↑ Kaufmann, Stefan H. E. (April 3, 2019). "Immunology's Coming of Age". Frontiers in Immunology . 10: 684. doi: 10.3389/fimmu.2019.00684 . PMC 6456699 . PMID 31001278.
1 2 Ross, Sarah H.; Cantrell, Doreen A. (April 18, 2019). "Signaling and Function of Interleukin-2 in T Lymphocytes". Annual Review of Immunology . 36: 411–433. doi:10.1146/annurev-immunol-042617-053352. PMC 6472684 . PMID 29677473.
↑ "Weill Cornell Researchers Develop New Treatment Regimen for HIV-Positive Patients". Weill Cornell Medicine. March 19, 1999.
↑ "Weill Cornell Studies Reveal Accelerated Improvement of Immune System and Antiviral Reactivity in Chronic HIV Infection". NewYork-Presbyterian. November 14, 2000.

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[1] Smith, Kendall A (2017-09-06). Molecular Immunity. WORLD SCIENTIFIC. doi:10.1142/10755. ISBN 978-981-323-170-2.

[2] "Loop | Kendall Arthur Smith". loop.frontiersin.org. Retrieved 2021-06-02.

[3] "Faculty | Weill Department of Medicine". medicine.weill.cornell.edu. Retrieved 2021-06-02.

[4] University, Denison. "Kendall A. Smith". Denison University Alumni. Retrieved 2021-06-02.

[5] Kaufmann, Stefan H. E. (April 3, 2019). "Immunology's Coming of Age". Frontiers in Immunology . 10: 684. doi: 10.3389/fimmu.2019.00684 . PMC 6456699 . PMID 31001278.

[:0-6] 1 2 Ross, Sarah H.; Cantrell, Doreen A. (April 18, 2019). "Signaling and Function of Interleukin-2 in T Lymphocytes". Annual Review of Immunology . 36: 411–433. doi:10.1146/annurev-immunol-042617-053352. PMC 6472684 . PMID 29677473.

[7] "Weill Cornell Researchers Develop New Treatment Regimen for HIV-Positive Patients". Weill Cornell Medicine. March 19, 1999.

[8] "Weill Cornell Studies Reveal Accelerated Improvement of Immune System and Antiviral Reactivity in Chronic HIV Infection". NewYork-Presbyterian. November 14, 2000.

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