Kim D. Janda (born August 23, 1957) is an American

chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a graduated scientist trained in the study of chemistry, or an officially enrolled student in the field. Chemists study the composition of ...

whose research focuses on the fields of

medicinal chemistry Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with drug design, designing and developing pharmaceutical medication, drugs. Medicinal chemistry involves the identification, ...

molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

immunology Immunology is a branch of biology and medicine that covers the study of Immune system, immune systems in all Organism, organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in ...

and

neuropharmacology Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmac ...

. Janda currently holds the rank of the Ely R. Callaway, Jr. Chaired

Professor Professor (commonly abbreviated as Prof.) is an Academy, academic rank at university, universities and other tertiary education, post-secondary education and research institutions in most countries. Literally, ''professor'' derives from Latin ...

in the Departments of

Chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...

and

Immunology Immunology is a branch of biology and medicine that covers the study of Immune system, immune systems in all Organism, organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in ...

The Scripps Research Institute Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, tec ...

(TSRI) in

La Jolla La Jolla ( , ) is a hilly, seaside neighborhood in San Diego, California, occupying of curving coastline along the Pacific Ocean. The population reported in the 2010 census was 46,781. The climate is mild, with an average daily temperature o ...

California California () is a U.S. state, state in the Western United States that lies on the West Coast of the United States, Pacific Coast. It borders Oregon to the north, Nevada and Arizona to the east, and shares Mexico–United States border, an ...

, 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 The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

First Award (1990),

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 program is one of the oldest of its kind in the United States. ...

(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 The University of Arizona (Arizona, U of A, UArizona, or UA) is a Public university, public Land-grant university, land-grant research university in Tucson, Arizona, United States. Founded in 1885 by the 13th Arizona Territorial Legislature, it ...

and obtained a M.S. in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

(1983) and a Ph.D. in 1984. He carried out postdoctoral research with

Richard Lerner Richard Alan Lerner (August 26, 1938 – December 2, 2021) was an American research chemist. He was best known for his work on catalytic antibodies and combinatorial antibody libraries. Lerner served as President of The Scripps Research Inst ...

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. 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 The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

to target

drug addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. Janda demonstrated that one could manipulate the immune system to generate antibodies against

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

. 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 (; or lenomorelin, INN) is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrel ...

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

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

s and

oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase ...

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

nornicotine Nornicotine is an alkaloid found in various plants including ''Nicotiana'', the tobacco plant. It is chemically similar to nicotine, but does not contain a methyl group. It is a precursor to the carcinogen N-Nitrosonornicotine, ''N''-nitrosonorni ...

, a constituent of

tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

, 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 use disorder; additionally nornicotine also catalyzes the covalent modification of certain prescription drugs such as the commonly used steroid,

prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

. 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 Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

disease. More recently, Janda’s group has found that nornicotine can also catalyze the isomerization of

retinal Retinal (also known as retinaldehyde) is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision). Some microorganisms use ret ...

molecules, implicating nornicotine in the pathology of both age-related

macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred vision, blurred or vision loss, no vision in the center of the visual field. Early on there are often no sym ...

as well as smoking-related developmental abnormalities. Lastly, his group has linked this glycation process to

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

addiction.

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 In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain i ...

and

Gram negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists of ...

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

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. His group has demonstrated that a synthetically prepared cell-surface glyco

sphingolipid Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sp ...

can be utilized as a panning reagent to identify fully human single chain antibodies (scFvs) that are selective for

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

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

External links

Janda Group Homepage at The Scripps Research Institute

Kim D. Janda's list of publications

References

{{DEFAULTSORT:Janda, Kim 21st-century American chemists American immunologists Scripps Research faculty Living people 1957 births