Kim Janda
Encyclopedia
Kim D. Janda is an American
chemist
who studies on 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).
and obtained a M.S. in Organic Chemistry
(1983) and a Ph.D. in 1984. He carried out postdoctoral research at the Research Institute of Scripps Clinic (which would later become The Scripps Research Institute), where he remained, becoming a full professor in 1996.
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 and obesity
. Janda demonstrated that one could manipulate the immune system to generate antibodies against cocaine
. He has demonstrated that antibodies resulting from this approach can protect from the lethal effects of cocaine overdose, even when administered after cocaine exposure. Recently, he detailed the treatment of cocaine addiction with viruses. 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.
s and oligonucleotide
s can be performed in a routine manner. His group has also demonstrated a technology termed “recursive deconvolution of combinatorial libraries” and "liquid phase combinatorial synthesis" which showed that reactants, products and by-products can be effectively “tagged” and targeted to different phases,.
, a constituent of tobacco
, can catalyze aldol reactions in water: the only known example of a metabolite capable of serving as a catalyst. 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 abuse; additionally nornicotine also catalyzes the covalent modification of certain prescription drugs such as the commonly used steroid, prednisone
. 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. 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. Lastly, his group has linked this glycation process to methamphetamine
addiction.
. 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. The Janda laboratory has also identified a scFv specific for the integrin α3β1 that is internalized by human pancreatic cancer cells; subsequent studies have employed this antibody conjugated with the potent cytotoxic compound duocarmycin SA for the selective delivery of chemotherapeutic agents.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
who studies on medicinal chemistry
Medicinal chemistry
Medicinal chemistry and pharmaceutical chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where it is involved with design, chemical synthesis and development for market of pharmaceutical...
, molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, immunology
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
and neuropharmacology
Neuropharmacology
Neuropharmacology is the study of how drugs affect cellular function in the nervous system. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior , including the study of how drug dependence...
.
Janda currently holds the rank of the Ely R. Callaway, Jr. Chaired Professor
Professor
A professor is a scholarly teacher; the precise meaning of the term varies by country. Literally, professor derives from Latin as a "person who professes" being usually an expert in arts or sciences; a teacher of high rank...
in the Departments of Chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
and Immunology
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
at The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...
(TSRI) in La Jolla, California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
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
Sloan Fellowship
The Sloan Research Fellowships are awarded annually by the Alfred P. Sloan Foundation since 1955 to "provide support and recognition to early-career scientists and scholars". This is distinct from the Sloan Fellows in business....
(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 ArizonaUniversity of Arizona
The University of Arizona is a land-grant and space-grant public institution of higher education and research located in Tucson, Arizona, United States. The University of Arizona was the first university in the state of Arizona, founded in 1885...
and obtained a M.S. in Organic Chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
(1983) and a Ph.D. in 1984. He carried out postdoctoral research at the Research Institute of Scripps Clinic (which would later become The Scripps Research Institute), where he remained, becoming a full professor in 1996.
Immunology
Janda’s independent career started working on catalytic antibodies. In 1993, his group described for the first time how a catalytic antibody can reroute a chemically disfavored reaction to give an endo Diels-Alder cyclization product rather than the uncatalyzed exo product. A second research infusion in this area attributable to Janda was the elucidation of the concept of reactive immunization.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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to target drug addiction and obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
. Janda demonstrated that one could manipulate the immune system to generate antibodies against cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
. He has demonstrated that antibodies resulting from this approach can protect from the lethal effects of cocaine overdose, even when administered after cocaine exposure. Recently, he detailed the treatment of cocaine addiction with viruses. Janda and colleagues then showed that an active vaccine against the orexigenic hormone ghrelin
Ghrelin
Ghrelin is a 28 amino acid peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone...
can slow the rate of weight gain, and adiposity, and do this through an entirely metabolic mechanism, as food intake was unchanged.
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 peptidePeptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s and oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
s can be performed in a routine manner. His group has also demonstrated a technology termed “recursive deconvolution of combinatorial libraries” and "liquid phase combinatorial synthesis" which showed that reactants, products and by-products can be effectively “tagged” and targeted to different phases,.
Nornicotine
The Janda laboratory demonstrated that nornicotineNicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
, a constituent of tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
, can catalyze aldol reactions in water: the only known example of a metabolite capable of serving as a catalyst. 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 abuse; additionally nornicotine also catalyzes the covalent modification of certain prescription drugs such as the commonly used steroid, prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
. 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. More recently, Janda’s group has found that nornicotine can also catalyze the isomerization of retinal
Retinal
Retinal, also called retinaldehyde or vitamin A aldehyde, is one of the many forms of vitamin A . Retinal is a polyene chromophore, and bound to proteins called opsins, is the chemical basis of animal vision...
molecules, implicating nornicotine in the pathology of both age-related macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
as well as smoking-related developmental abnormalities. Lastly, his group has linked this glycation process to methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
addiction.
Cell-to-cell communication
Janda’s group has also begun explorations in the area of cell-to-cell communication. He groups 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. 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. By panning this library against a B lymphoctye cell line, a unique cell-binding and internalizing peptide was discovered. Further mechanistic studies of this peptide uncovered a dimerization “switch” that modulates the cell-penetrating activity. In addition to these studies, Janda has also examined the development of effective immunotherapies for the treatment of cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. His group has demonstrated that a synthetically prepared cell-surface glycosphingolipid
Sphingolipid
Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named for the mythological Sphinx because of their enigmatic nature. These compounds play...
can be utilized as a panning reagent to identify fully human single chain antibodies (scFvs) that are selective for melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and breast tumor cells. The Janda laboratory has also identified a scFv specific for the integrin α3β1 that is internalized by human pancreatic cancer cells; subsequent studies have employed this antibody conjugated with the potent cytotoxic compound duocarmycin SA for the selective delivery of chemotherapeutic agents.
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