Kim Janda

Kim D. Janda (born August 23, 1957) is an American chemist whose research focuses on the fields of medicinal chemistry, molecular biology, immunology and neuropharmacology.

Janda currently holds the rank of the Ely R. Callaway, Jr. Chaired Professor in the Departments of Chemistry and Immunology at The Scripps Research Institute (TSRI) in La Jolla, California, and is also the director of the Worm Institute of Research and Medicine (WIRM) and a Skaggs Scholar within the Skaggs Institute of Chemical Biology, both at TSRI. He has been the recipient of numerous awards including an NIH First Award (1990), Sloan Fellowship (1993) and the Arthur C. Cope Scholar Award (1999).

Education

Janda obtained a B.S. in clinical chemistry from the University of South Florida in 1980. He then studied at the University of Arizona and obtained a M.S. in organic chemistry (1983) and a Ph.D. in 1984. He carried out postdoctoral research with Richard Lerner at the Research Institute of Scripps Clinic (which would later become The Scripps Research Institute), where he remained, becoming a full professor in 1996.

Research

= Immunology =

Janda's independent career started working on catalytic antibodies. In 1993, his group was the first to describe how a catalytic antibody can reroute a chemically disfavored reaction to give an endo Diels-Alder cyclization product rather than the uncatalyzed exo product.{{cite journal|last1=Janda|first1=K.|last2=Shevlin|first2=C.|last3=Lerner|first3=R.|title=Antibody catalysis of a disfavored chemical transformation|journal=Science|date=22 January 1993|volume=259|issue=5094|pages=490–493|doi=10.1126/science.8424171|pmid=8424171|bibcode=1993Sci...259..490J}} A second research infusion in this area attributable to Janda was the elucidation of the concept of reactive immunization.{{cite journal|last1=Wirsching|first1=P.|last2=Ashley|first2=J. A.|last3=Lo|first3=C.-H. L.|last4=Janda|first4=K. D.|last5=Lerner|first5=R. A.|title=Reactive Immunization|journal=Science|date=15 December 1995|volume=270|issue=5243|pages=1775–1783|doi=10.1126/science.270.5243.1775|pmid=8525366|bibcode=1995Sci...270.1775W|s2cid=36700296}}

A second area of research Janda's group has pioneered is the field of "immunopharmacotherapy" a term coined by Janda's laboratory to describe the use of the immune system to target drug addiction{{cite news

| title=An Addiction Vaccine, Tantalizingly Close

| author=Douglas Quenqua

| url=https://www.nytimes.com/2011/10/04/health/04vaccine.html?hp

| newspaper=New York Times

| date=October 3, 2011

}}{{Cite journal|last1=Lin|first1=Mingliang|last2=Lee|first2=Jinny Claire|last3=Blake|first3=Steven|last4=Ellis|first4=Beverly|last5=Eubanks|first5=Lisa M.|last6=Janda|first6=Kim D.|date=2021-01-25|title=Broadly Neutralizing Synthetic Cannabinoid Vaccines|journal=JACS Au|volume=1|issue=1|pages=31–40|doi=10.1021/jacsau.0c00057|pmid=34467269|pmc=8395583|doi-access=free}} and obesity. Janda demonstrated that one could manipulate the immune system to generate antibodies against cocaine.{{cite journal|last1=Carrera|first1=M. Rocío A.|last2=Ashley|first2=Jon A.|last3=Parsons|first3=Loren H.|last4=Wirsching|first4=Peter|last5=Koob|first5=George F.|last6=Janda|first6=Kim D.|title=Suppression of psychoactive effects of cocaine by active immunization|journal=Nature|date=14 December 1995|volume=378|issue=6558|pages=727–730|doi=10.1038/378727a0|pmid=7501020|bibcode=1995Natur.378..727C|s2cid=4314332}} He has demonstrated that antibodies resulting from this approach can protect from the lethal effects of cocaine overdose, even when administered after cocaine exposure.{{cite journal|last1=Carrera|first1=M. Rocío A.|last2=Trigo|first2=José Manuel|last3=Wirsching|first3=Peter|last4=Roberts|first4=Amanda J.|last5=Janda|first5=Kim D.|title=Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose|journal=Pharmacology Biochemistry and Behavior|date=August 2005|volume=81|issue=4|pages=709–714|doi=10.1016/j.pbb.2005.04.018|pmid=16005948|s2cid=20241635}} Recently, he detailed the treatment of cocaine addiction with viruses.{{cite journal|last1=Carrera|first1=M. R. A.|last2=Kaufmann|first2=G. F.|last3=Mee|first3=J. M.|last4=Meijler|first4=M. M.|last5=Koob|first5=G. F.|last6=Janda|first6=K. D.|title=Treating cocaine addiction with viruses|journal=Proceedings of the National Academy of Sciences|date=28 June 2004|volume=101|issue=28|pages=10416–10421|doi=10.1073/pnas.0403795101|bibcode=2004PNAS..10110416C|pmc=478586|pmid=15226496|doi-access=free}} Janda and colleagues then showed that an active vaccine against the orexigenic hormone ghrelin can slow the rate of weight gain, and adiposity, and do this through an entirely metabolic mechanism, as food intake was unchanged.{{cite journal|last1=Zorrilla|first1=E. P.|last2=Iwasaki|first2=S.|last3=Moss|first3=J. A.|last4=Chang|first4=J.|last5=Otsuji|first5=J.|last6=Inoue|first6=K.|last7=Meijler|first7=M. M.|last8=Janda|first8=K. D.|title=Vaccination against weight gain|journal=Proceedings of the National Academy of Sciences|date=4 August 2006|volume=103|issue=35|pages=13226–13231|doi=10.1073/pnas.0605376103|pmid=16891413|pmc=1559781|bibcode=2006PNAS..10313226Z|doi-access=free}}

=Encoded combinatorial libraries=

Another area of medicinal research in which the Janda laboratory has made contributions encompasses techniques to create molecular diversity, uncover active components from complex mixtures and the separation of synthetic targets by phase tagging. He has published methodologies that allow implementation of what has been termed "encoded combinatorial libraries", providing a means whereby the alternating parallel synthesis of peptides and oligonucleotides can be performed in a routine manner.{{cite journal|last1=Nielsen|first1=John|last2=Brenner|first2=Sydney|last3=Janda|first3=Kim D.|title=Synthetic methods for the implementation of encoded combinatorial chemistry|journal=Journal of the American Chemical Society|date=October 1993|volume=115|issue=21|pages=9812–9813|doi=10.1021/ja00074a063|bibcode=1993JAChS.115.9812N }} His group has also demonstrated a technology termed "recursive deconvolution of combinatorial libraries"{{cite journal|last1=Erb|first1=E.|last2=Janda|first2=K. D.|last3=Brenner|first3=S.|title=Recursive deconvolution of combinatorial chemical libraries.|journal=Proceedings of the National Academy of Sciences|date=22 November 1994|volume=91|issue=24|pages=11422–11426|doi=10.1073/pnas.91.24.11422|bibcode=1994PNAS...9111422E|pmc=45243|pmid=7972077|doi-access=free}} and "liquid phase combinatorial synthesis"{{cite journal|last1=Han|first1=H.|last2=Wolfe|first2=M. M.|last3=Brenner|first3=S.|last4=Janda|first4=K. D.|title=Liquid-phase combinatorial synthesis.|journal=Proceedings of the National Academy of Sciences|date=3 July 1995|volume=92|issue=14|pages=6419–6423|doi=10.1073/pnas.92.14.6419|bibcode=1995PNAS...92.6419H|pmc=41529|pmid=7541541|doi-access=free}} which showed that reactants, products and by-products can be effectively "tagged" and targeted to different phases,.

=Nornicotine=

The Janda laboratory demonstrated that nornicotine, a constituent of tobacco, can catalyze aldol reactions in water: the only known example of a metabolite capable of serving as a catalyst.{{cite journal|last1=Dickerson|first1=Tobin J.|last2=Lovell|first2=Timothy|last3=Meijler|first3=Michael M.|last4=Noodleman|first4=Louis|last5=Janda|first5=Kim D.|title=Nornicotine Aqueous Aldol Reactions: Synthetic and Theoretical Investigations into the Origins of Catalysis|journal=The Journal of Organic Chemistry|date=October 2004|volume=69|issue=20|pages=6603–6609|doi=10.1021/jo048894j|pmid=15387581}} This finding has led him to propose new chemical links between smoking and metabolic diseases, including that nornicotine causes aberrant protein glycation and thus provides an unrecognized pathway for the development of the pathology of tobacco use disorder; additionally nornicotine also catalyzes the covalent modification of certain prescription drugs such as the commonly used steroid, prednisone.{{cite journal|last1=Dickerson|first1=T. J.|last2=Janda|first2=K. D.|title=A previously undescribed chemical link between smoking and metabolic disease|journal=Proceedings of the National Academy of Sciences|date=28 October 2002|volume=99|issue=23|pages=15084–15088|doi=10.1073/pnas.222561699|pmid=12403823|pmc=137547|bibcode=2002PNAS...9915084D|doi-access=free}} These findings were crucial to his group’s publication on the glycation of the amyloid β-peptide by nornicotine, proposing the hypothesis that there is a fortuitous chemical dynamic between smoking and Alzheimer's disease.{{cite journal|last1=Dickerson|first1=T. J.|last2=Janda|first2=K. D.|title=Glycation of the amyloid -protein by a nicotine metabolite: A fortuitous chemical dynamic between smoking and Alzheimer's disease|journal=Proceedings of the National Academy of Sciences|date=18 June 2003|volume=100|issue=14|pages=8182–8187|doi=10.1073/pnas.1332847100|pmid=12815102|pmc=166203|bibcode=2003PNAS..100.8182D|doi-access=free}} More recently, Janda’s group has found that nornicotine can also catalyze the isomerization of retinal molecules, implicating nornicotine in the pathology of both age-related macular degeneration as well as smoking-related developmental abnormalities.{{cite journal|last1=Brogan|first1=A. P.|last2=Dickerson|first2=T. J.|last3=Boldt|first3=G. E.|last4=Janda|first4=K. D.|title=Altered retinoid homeostasis catalyzed by a nicotine metabolite: Implications in macular degeneration and normal development|journal=Proceedings of the National Academy of Sciences|date=13 July 2005|volume=102|issue=30|pages=10433–10438|doi=10.1073/pnas.0504721102|pmid=16014706|pmc=1180800|bibcode=2005PNAS..10210433B|doi-access=free}} Lastly, his group has linked this glycation process to methamphetamine addiction.{{cite journal|last1=Dickerson|first1=Tobin J.|last2=Yamamoto|first2=Noboru|last3=Ruiz|first3=Diana I.|last4=Janda|first4=Kim D.|title=Immunological Consequences of Methamphetamine Protein Glycation|journal=Journal of the American Chemical Society|date=September 2004|volume=126|issue=37|pages=11446–11447|doi=10.1021/ja047690h|pmid=15366884|bibcode=2004JAChS.12611446D }}

=Cell-to-cell communication=

Janda’s group has also begun explorations in the area of cell-to-cell communication. His group was the first to report a successful chemical synthesis of AI-2, a compound that is employed by both Gram positive and Gram negative bacteria for interspecies communication.{{cite journal|last1=Meijler|first1=Michael M.|last2=Hom|first2=Louis G.|last3=Kaufmann|first3=Gunnar F.|last4=McKenzie|first4=Kathleen M.|last5=Sun|first5=Chengzao|last6=Moss|first6=Jason A.|last7=Matsushita|first7=Masayuki|last8=Janda|first8=Kim D.|title=Synthesis and Biological Validation of a Ubiquitous Quorum-Sensing Molecule|journal=Angewandte Chemie International Edition|date=13 April 2004|volume=43|issue=16|pages=2106–2108|doi=10.1002/anie.200353150|pmid=15083457}} The completion of the synthesis has allowed the validation of a boronate ester complex of AI-2 as the active signaling species in the symbiotic bacteria V. harveyi.

=Cancer therapy=

Janda has also worked creating peptide and antibody molecules for the treatment of cancer. By employing a novel approach, he was able to access and screen a wide range of proteins using both sequence space and conformational space.{{cite journal|last1=Gao|first1=C.|last2=Mao|first2=S.|last3=Lo|first3=C.-H. L.|last4=Wirsching|first4=P.|last5=Lerner|first5=R. A.|last6=Janda|first6=K. D.|title=Making artificial antibodies: A format for phage display of combinatorial heterodimeric arrays|journal=Proceedings of the National Academy of Sciences|date=25 May 1999|volume=96|issue=11|pages=6025–6030|doi=10.1073/pnas.96.11.6025|pmid=10339535|pmc=26829|bibcode=1999PNAS...96.6025G|doi-access=free}} By panning this library against a B lymphoctye cell line, a unique cell-binding and internalizing peptide was discovered.{{cite journal|last1=Gao|first1=Changshou|last2=Mao|first2=Shenlan|last3=Ditzel|first3=Henrik J.|last4=Farnaes|first4=Lauge|last5=Wirsching|first5=Peter|last6=Lerner|first6=Richard A.|last7=Janda|first7=Kim D.|title=A cell-penetrating peptide from a novel pVII–pIX phage-displayed random peptide library|journal=Bioorganic & Medicinal Chemistry|date=December 2002|volume=10|issue=12|pages=4057–4065|doi=10.1016/S0968-0896(02)00340-1|pmid=12413859}} Further mechanistic studies of this peptide uncovered a dimerization "switch" that modulates the cell-penetrating activity.{{cite journal|last1=Moss|first1=Jason A.|last2=Lillo|first2=Antonietta|last3=Kim|first3=Young Soo|last4=Gao|first4=Changshou|last5=Ditzel|first5=Henrik|last6=Janda|first6=Kim D.|title=A Dimerization "Switch" in the Internalization Mechanism of a Cell-Penetrating Peptide|journal=Journal of the American Chemical Society|date=January 2005|volume=127|issue=2|pages=538–539|doi=10.1021/ja0443171|pmid=15643874|bibcode=2005JAChS.127..538M }} In addition to these studies, Janda has also examined the development of effective immunotherapies for the treatment of cancer. His group has demonstrated that a synthetically prepared cell-surface glycosphingolipid can be utilized as a panning reagent to identify fully human single chain antibodies (scFvs) that are selective for melanoma and breast tumor cells.{{cite journal|last1=Lee|first1=Kyung Joo|last2=Mao|first2=Shenlan|last3=Sun|first3=Chengzao|last4=Gao|first4=Changshou|last5=Blixt|first5=Ola|last6=Arrues|first6=Sandra|last7=Hom|first7=Louis G.|last8=Kaufmann|first8=Gunnar F.|last9=Hoffman|first9=Timothy Z.|last10=Coyle|first10=Avery R.|last11=Paulson|first11=James|last12=Felding-Habermann|first12=Brunhilde|last13=Janda|first13=Kim D.|title=Phage-Display Selection of a Human Single-Chain Fv Antibody Highly Specific for Melanoma and Breast Cancer Cells Using a Chemoenzymatically Synthesized G−Carbohydrate Antigen|journal=Journal of the American Chemical Society|date=October 2002|volume=124|issue=42|pages=12439–12446|doi=10.1021/ja020737j|pmid=12381184|bibcode=2002JAChS.12412439L }} The Janda laboratory has also identified a scFv specific for the integrin α₃β₁ that is internalized by human pancreatic cancer cells;{{cite journal|last1=Gao|first1=Changshou|last2=Mao|first2=Shenlan|last3=Ronca|first3=Francesca|last4=Zhuang|first4=Sufei|last5=Quaranta|first5=Vito|last6=Wirsching|first6=Peter|last7=Janda|first7=Kim D|title=De novo identification of tumor-specific internalizing human antibody–receptor pairs by phage-display methods|journal=Journal of Immunological Methods|date=March 2003|volume=274|issue=1–2|pages=185–197|doi=10.1016/S0022-1759(02)00522-7|pmid=12609544}} subsequent studies have employed this antibody conjugated with the potent cytotoxic compound duocarmycin SA for the selective delivery of chemotherapeutic agents.{{cite journal|last1=Lillo|first1=Antonietta M|last2=Sun|first2=Chengzao|last3=Gao|first3=Changshou|last4=Ditzel|first4=Henrik|last5=Parrish|first5=Jay|last6=Gauss|first6=Carla-Marie|last7=Moss|first7=Jason|last8=Felding-Habermann|first8=Brunhilde|last9=Wirsching|first9=Peter|last10=Boger|first10=Dale L|last11=Janda|first11=Kim D|title=A Human Single-Chain Antibody Specific for Integrin α3β1 Capable of Cell Internalization and Delivery of Antitumor Agents|journal=Chemistry & Biology|date=July 2004|volume=11|issue=7|pages=897–906|doi=10.1016/j.chembiol.2004.04.018|pmid=15271348|doi-access=free}}

Professional awards and associations

Member of the Board of Trustees, The Skaggs Institute for Research, 2006
Arthur C. Cope Scholar Award, 1999
Alfred P. Sloan Fellowship, 1993–1995
NIH FIRST Award, 1990–1995
Fellow, American Institute of Chemists, 1986–present
American Chemical Society, 1981–present

External links

[https://www.scripps.edu/janda/ Janda Group Homepage at The Scripps Research Institute]
[https://www.scripps.edu/janda/ewExternalFiles/KDJanda_biblio_2023.pdf Kim D. Janda's list of publications]