Ajit Varki

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Ajit Varki is a physician-scientist who is distinguished professor of medicine and cellular and molecular medicine, founding co-director of the Glycobiology Research and Training Center [1] at the University of California, San Diego (UCSD), and founding co-director of the UCSD/Salk Center for Academic Research and Training in Anthropogeny (CARTA). [2] He is also executive editor of the textbook Essentials of Glycobiology [3] and distinguished visiting professor at the Indian Institute of Technology in Madras and the National Center for Biological Sciences in Bangalore. He is a specialist advisor to the Human Gene Nomenclature Committee.

Contents

Education and biography

Varki went to the Bishop Cotton Boys' School, Bangalore, India during which time he was also strongly influenced by his maternal grandfather Pothan Joseph, a famous journalist and founding editor of many Indian newspapers, including Deccan Herald. He went on to receive basic training in physiology, medicine, biology, and biochemistry at the Christian Medical College, Vellore, continuing to maintain the first rank in his class throughout his schooling. He then did postgraduate training at the University of Nebraska and Washington University School of Medicine, leading to board certification in internal medicine, hematology, and oncology. Following a postdoctoral fellowship with Stuart Kornfeld in St. Louis, he joined the faculty of UCSD in 1982. Significant past appointments include: associate dean for physician-scientist training, [4] co-head, Division of Hematology/Oncology, UCSD (1987–89), the interim directorship of the UCSD Cancer Center (1996–97), scientific advisor to the Complex Carbohydrate Research Center (University of Georgia), the Yerkes Primate Center (Emory University), member of the National Advisory Committee of PubMed Central (NLM/NIH), and coordinator for the multidisciplinary UCSD Project for Explaining the Origin of Humans.[ citation needed ]

Research interests

The research group led by Varki has made many contributions over the last few decades [5] towards understanding the biological roles of the sugar chains or "glycans" found on all vertebrate cell surfaces and glycoproteins. In this field of Glycobiology, his present focus is on the Sialic Acids, which are found at the outermost position on such glycans, and which can be recognized by intrinsic receptors such as Selectins and the Siglecs (which he co-discovered and named as a sub-group of I-type Lectins), and also by the binding proteins of various pathogens. The group studies the significance of these interactions in biology, evolution and disease. [6] A particular focus is on multiple differences in sialic acid biology between humans and our closest evolutionary cousins, the great apes. These represent unusual events that occurred during human evolution and are relevant to understanding aspects of human uniqueness in health and disease. [7]

General interests

Varki has emphasized the key role of Physician-Scientists in the success of the US biomedical enterprise, and advocated for the support and preservation of this track at the national level. [8] He also played a key role in advocating for a chimpanzee genome project, [9] while emphasizing the need for ethical treatment of chimpanzees in research. [10] He continues to advocate for and facilitate interactions amongst scientists with interests in explaining the origin of the human species. In this regard, he coined the term "Phenome", in the context of recommending a "Great Ape Phenome Project". [11] While Editor-in-Chief of the Journal of Clinical Investigation , Varki made it the first major biomedical journal to be freely available on the web in 1996, presaging the general "Open Access" movement that came years later. [12] He also created the first viable model for a major Open Access textbook, the 2nd. Edition of the textbook Essentials of Glycobiology. [3] Varki is also very concerned about improving the support systems for women who pursue academic scientific careers, while also wishing to bear children. Varki and his wife Nissi enjoy entertaining, including a Christmas Carols celebration serving Tandoori goose.

Open Access

While Editor-in-Chief of the Journal of Clinical Investigation , Varki made it the first major biomedical journal to be freely available on the web in 1996. [13] Varki wrote, "The vexing issue of the day is how to appropriately charge users for this electronic access. The nonprofit nature of the JCI allows consideration of a truly novel solution — not to charge anyone at all!". [14] As executive editor of Essentials of Glycobiology, Varki also made it the first major biomedical textbook that was fully open access. [15]

Diet and disease

Varki's group has recently shown that a diet rich in red meat can result in accumulation of a non-human sialic acid molecule called Neu5Gc ("Gc") in the intestines and other tissues. This can allow type of dangerous E.coli toxin to affect the human body. [16] Also, humans develop antibodies against this foreign Gc molecule, increasing the risk of diseases like cancer. [17]

Mind Over Reality Transition (MORT)

Varki developed an idea proposed in 2005 by the late Danny Brower of the University of Arizona into a theory called Mind Over Reality Transition (MORT) which has been published in two letters [18] [19] and two books. [20] [21] MORT proposes an evolutionary mechanism to explain the emergence of behaviorally modern humans and some of their unique behaviors including an extended theory of mind and a tendency to deny reality.

Honors

Varki is an elected member of the American Academy of Arts and Sciences, [22] the Institute of Medicine, [23] the American Society for Clinical Investigation, [24] and the Association of American Physicians. He is recipient of a MERIT award from the NIH, [25] an American Cancer Society Faculty Research Award, and the two highest honors in the field of glycobiology, the Karl Meyer Award of the Society for Glycobiology (2005) [26] and the International Glycoconjugate Organization (IGO) Award (2007). [27] He was also elected to serve as president of the Society for Glycobiology (1996), [28] Editor-in-Chief of the Journal of Clinical Investigation (1992–97), [29] and president of the American Society for Clinical Investigation (1998–99). [30]

Selected publications

Beyond his primary research accomplishments, Varki has written many widely cited and influential review articles, commentaries and letters on a variety of topics. Some examples are listed below. His publications have been cited more than 60,000 times and he has an h-index of 122. [31]

See also

Related Research Articles

<span class="mw-page-title-main">Sialic acid</span> Class of chemical compounds

Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is N-acetylneuraminic acid found in animals and some prokaryotes.

Siglecs(Sialic acid-binding immunoglobulin-type lectins) are cell surface proteins that bind sialic acid. They are found primarily on the surface of immune cells and are a subset of the I-type lectins. There are 14 different mammalian Siglecs, providing an array of different functions based on cell surface receptor-ligand interactions.

<span class="mw-page-title-main">CD22</span> Lectin molecule

CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases.

<span class="mw-page-title-main">CD33</span> Mammalian protein found in Homo sapiens

CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

<span class="mw-page-title-main">SIGLEC7</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 7 is a protein that in humans is encoded by the SIGLEC7 gene. SIGLEC7 has also been designated as CD328.

<span class="mw-page-title-main">Sialic acid-binding Ig-like lectin 12</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 12, or Siglec-XII, is a protein that in humans, is encoded by the SIGLEC12 gene.

<span class="mw-page-title-main">SIGLEC5</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 5 is a protein that in humans is encoded by the SIGLEC5 gene. SIGLEC5 has also been designated CD170.

<span class="mw-page-title-main">SIGLEC9</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 9 is a protein that in humans is encoded by the SIGLEC9 gene.

Anthropogeny is the study of human origins. It is not simply a synonym for human evolution by natural selection, which is only a part of the processes involved in human origins. Many other factors besides natural selection were involved, ranging over climatic, geographic, ecological, social, and cultural ones. Anthropogenesis, meaning the process or point of becoming human, is also called hominization.

<span class="mw-page-title-main">SIGLEC8</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 8 is a protein that in humans is encoded by the SIGLEC8 gene. This gene is located on chromosome 19q13.4, about 330 kb downstream of the SIGLEC9 gene. Within the siglec family of transmembrane proteins, Siglec-8 belongs to the CD33-related siglec subfamily, a subfamily that has undergone rapid evolution.

<span class="mw-page-title-main">SIGLEC10</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 10 is a protein that in humans is encoded by the SIGLEC10 gene. Siglec-G is often referred to as the murine paralog of human Siglec-10

In biochemistry, the term sialome may refer to two distinct concepts:

<span class="mw-page-title-main">Center for Academic Research and Training in Anthropogeny</span>

The Center for Academic Research and Training in Anthropogeny (CARTA) is a center at the University of California, San Diego. Formally established in 2008, CARTA is a collaboration between faculty members of UC San Diego main campus, the UCSD School of Medicine, the Salk Institute for Biological Studies, and interested scientists at other institutions from around the world.

<i>N</i>-Glycolylneuraminic acid Chemical compound

N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid molecule found in most non-human mammals. Humans cannot synthesize Neu5Gc because the human gene CMAH is irreversibly mutated, though it is found in other apes. The gene CMAH encodes for CMP-N-acetylneuraminic acid hydroxylase, which is the enzyme responsible for CMP-Neu5Gc from CMP-N-acetylneuraminic (CMP-Neu5Ac) acid. This loss of CMAH is estimated to have occurred 2-3 million years ago, just before the emergence of the genus Homo.

Jeffrey David Esko, Ph.D.,M.D. (h.c) is currently a Distinguished Professor of Cellular and Molecular Medicine and Co-Director of the Glycobiology Research and Training Center at the University of California, San Diego. His research has focuses on understanding the structure, biosynthesis and biological roles of proteoglycans in mammalian cells and model organisms. Esko popularized proteoglycans through his pioneering genetic and functional studies in cells and model organisms. He discovered the dependence of tumor formation on heparan sulfate, the first small molecule inhibitors of heparan sulfate, the action of proteoglycans as receptors for hepatic lipoprotein clearance and for delivery of therapeutic agents. Esko cofounded Zacharon Pharmaceuticals. He was an editor and author of the first textbook in the Glycobiology field, Essentials of Glycobiology.

Jamey Marth is a molecular and cellular biologist. He is currently on the faculty of the SBP Medical Discovery Institute in La Jolla, California where he is Director of the Immunity and Pathogenesis program.

Stuart Arthur Kornfeld is a professor of medicine at Washington University in St. Louis and researcher in glycobiology.

<span class="mw-page-title-main">SIGLEC6</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 6 is a protein that in humans is encoded by the SIGLEC6 gene. The gene was originally named CD33L (CD33-like) due to similarities between these genes but later became known as OB-BP1 due to its ability to bind to this factor and, finally, SIGLEC6 as the sixth member of the SIGLEC family of receptors to be identified. The protein has also been given the CD designation CD327.

Nicki Packer FRSC is a distinguished professor of glycoproteomics in the School of Natural Sciences at Macquarie University and principal research leader at Griffith University's Institute for Glycomics. Packer is a Fellow of the Royal Society of Chemistry and in 2021 received the Distinguished Achievement in Proteomic Sciences Award from the Human Proteome Organization. Her research focuses on biological functional of glycoconjugates by linking glycomics with proteomics and bioinformatics.

GlycoRNAs are small non-coding RNAs with sialylated glycans.

References

  1. ↑ "GRTC: About". United States: Glycobiology Research and Training Center. Archived from the original on February 13, 2012. Retrieved February 23, 2013.
  2. ↑ "Center for Academic Research Training in Anthropogeny (CARTA)". Carta.anthropogeny.org. Retrieved January 4, 2012.
  3. 1 2 Essentials of Glycobiology. Ncbi.nlm.nih.gov. October 3, 2011. ISBN   9780879695590 . Retrieved January 4, 2012.
  4. ↑ "UCSD Office of the Associate Dean for Physician-Scientist Training". Meded.ucsd.edu. Retrieved January 4, 2012.
  5. ↑ "San Diego Science Festival 2009 Nifty Fifty – Profile for Dr. Ajit Varki". Scholarnexus.com. May 23, 2007. Archived from the original on December 30, 2011. Retrieved January 4, 2012.
  6. ↑ "Varki Lab Website". Cmm.ucsd.edu. Archived from the original on February 13, 2012. Retrieved January 4, 2012.
  7. ↑ Bruce Lieberman (2008). "Human evolution: Details of being human". Nature. Nature.com. 454 (7200): 21–23. doi:10.1038/454021a. PMID   18596780. S2CID   205039194.
  8. ↑ Varki Ajit; Rosenberg Leon E (2002). "Emerging opportunities and career paths for the young physician-scientist". Nature Medicine. 8 (5): 437–439. doi:10.1038/nm0502-437. PMID   11984577. S2CID   8639414.
  9. ↑ Ajit Varki (August 1, 2000). "A Chimpanzee Genome Project Is a Biomedical Imperative. By Ajit Varki. Genome Res. 2000. 10: 1065–1070". Genome Research. Genome.cshlp.org. 10 (8): 1065–1070. doi: 10.1101/gr.10.8.1065 . PMID   10958623 . Retrieved January 4, 2012.
  10. ↑ Gagneux Pascal; Moore James J.; Varki Ajit (September 2005). "The ethics of research on great apes". Nature. 437 (7055): 27–29. Bibcode:2005Natur.437...27G. doi:10.1038/437027a. PMID   16136111. S2CID   11500691.
  11. ↑ Varki, A; Wills, C; Perlmutter, D; et al. (October 9, 1998). "Great Ape Phenome Project?". Science. 282 (5387): 239d–239. Bibcode:1998Sci...282..239V. doi:10.1126/science.282.5387.239d. PMID   9841385. S2CID   5837659 . Retrieved January 4, 2012.
  12. ↑ Savla U (2004). "Reflecting on 80 years of excellence". J. Clin. Invest. 114 (8): 1006–16. doi:10.1172/JCI23290. PMC   522269 . PMID   15489943.
  13. ↑ Savla, U (2004). "Reflecting on 80 years of excellence". J. Clin. Invest. 114 (8): 1006–16. doi:10.1172/JCI23290. PMC   522269 . PMID   15489943.
  14. ↑ Varki, A (1996). "The times they are still a'changing: keeping up with the times". J Clin Invest. 97 (1): 1. doi:10.1172/JCI118375. PMC   507053 . PMID   8550819.
  15. ↑ Varki A, Cummings R, Esko J, Freeze H, Stanley P, Bertozzi C, Hart G, Etzler M (2008). Essentials of glycobiology (2nd ed.). Cold Spring Harbor Laboratory Press. ISBN   978-0-87969-770-9. PMID   20301239.
  16. ↑ Kain, Debra (October 29, 2008). "Eating Red Meat Sets Up Target for Disease-Causing Bacteria". Ucsdnews.ucsd.edu. Retrieved January 4, 2012.
  17. ↑ Kain, Debra (November 13, 2008). "How Eating Red Meat Can Spur Cancer Progression". Ucsdnews.ucsd.edu. Archived from the original on February 12, 2012. Retrieved January 4, 2012.
  18. ↑ Varki, A. (2009). "Human uniqueness and the denial of death". Nature. 460 (7256): 684. Bibcode:2009Natur.460..684V. doi: 10.1038/460684c . PMID   19661895.
  19. ↑ Varki, A. (2016). "Why are there no persisting hybrids of humans with Denisovans, Neanderthals, or anyone else?". Proceedings of the National Academy of Sciences of the United States of America. 113 (17): E2354. Bibcode:2016PNAS..113E2354V. doi: 10.1073/pnas.1602270113 . PMC   4855598 . PMID   27044111.
  20. ↑ Varki, Ajit. (2013). Denial : self-deception, false beliefs, and the origins of the human mind. Brower, Danny L. (1st ed.). New York: Twelve. ISBN   9781455511914. OCLC   816563634.
  21. ↑ Varki, Ajit (2019), "Did Human Reality Denial Breach the Evolutionary Psychological Barrier of Mortality Salience? A Theory that Can Explain Unusual Features of the Origin and Fate of Our Species", in Shackelford, Todd K.; Zeigler-Hill, Virgil (eds.), Evolutionary Perspectives on Death, Evolutionary Psychology, Springer International Publishing, pp. 109–135, doi: 10.1007/978-3-030-25466-7_6 , ISBN   9783030254650
  22. ↑ "Academy Elects 225th Class of Fellows and Foreign Honorary Members". Amacad.org. April 26, 2005. Archived from the original on June 15, 2009. Retrieved January 4, 2012.
  23. ↑ "Institute of Medicine of the National Academies Directory – Ajit Varki". Iom.edu. Archived from the original on 2012-08-03. Retrieved January 4, 2012.
  24. ↑ "The American Society for Clinical Investigation Membership List". The-asci.org. Retrieved January 4, 2012.
  25. ↑ "New Initiative to Study the Glycobiology of Cancer Could Aid Understanding of Cancer Risk and Detection". Cancer.gov. August 22, 2007. Archived from the original on 2010-05-27. Retrieved January 4, 2012.
  26. ↑ "Karl Meyer Award Background and Past Winners". Glycobiology.org. Archived from the original on 2011-09-28. Retrieved January 4, 2012.
  27. ↑ "UCSD News. March 8, 2007. By Debra Kain. "UCSD's Ajit Varki to Receive Glycobiology's Highest International Honor"". Ucsdnews.ucsd.edu. March 8, 2007. Retrieved January 4, 2012.
  28. ↑ "Society for Glycobiology: Committees: Past Presidents". Glycobiology.org. Archived from the original on 2011-12-23. Retrieved January 4, 2012.
  29. ↑ Insel PA, Kornfeld S, Majerus PW, Marks AR, Marks PA, Relman AS, Scharschmidt BF, Stossel TP, Varki AP, Weiss SJ, Wilson JD (October 15, 2004). "Historical Highlights: Blasts from the past". Journal of Clinical Investigation. 114 (8): 1017–1033. doi:10.1172/JCI23321. PMC   522273 . PMID   15489944.
  30. ↑ "American Society for Clinical Investigation Council History". The-asci.org. Retrieved January 4, 2012.
  31. ↑ "Jorge Hirsch's research and public service page". Physics.ucsd.edu. Retrieved January 4, 2012.
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