Daniel A. Portnoy | |
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Born | 1956 |
Occupation(s) | academic, microbiologist |
Daniel A. Portnoy (born 1956 in Syracuse, NY) is a microbiologist, the Edward E. Penhoet Distinguished Chair in Global Public Health and Infectious Diseases, and a professor of biochemistry, Biophysics and Structural Biology in the Department of Molecular and Cell Biology and in the Division of Microbiology in the Department of Plant and Microbial Biology at the University of California, Berkeley. [1] He is one of the world's foremost experts on Listeria monocytogenes , the bacterium that causes the severe foodborne illness Listeriosis. He has made seminal contributions to multiple aspects of bacterial pathogenesis, cell biology, innate immunity, and cell mediated immunity using L. monocytogenes as a model system and has helped to push forward the use of attenuated L. monocytogenes as an immunotherapeutic tool in the treatment of cancer.
Dr. Portnoy got his start in microbiology in the lab of Dr. Sydney Rittenberg working on Bdellovibrio as an undergraduate at UCLA where he earned a B.A. in Bacteriology in 1978. He next earned his Ph.D. in 1983 under the tutelage of Stanley Falkow first at the University of Washington finishing at Stanford University. In the Falkow Lab, he worked on the conserved virulence plasmids in Yersinia enterocolitica , Yersinia pseudotuberculosis , and Yersiniapestis, [2] and discovered what turned out to be the first effectors of type III secretion. [3] To further his appreciation of host cells, he did his postdoctoral fellowship in the Zanvil Cohn Laboratory of Cellular Physiology and Immunology at the Rockefeller University in New York, working with Jay Unkeless and Jeff Ravetch. At Rockefeller University he worked on macrophage Fc receptors and lysosomal proteases.
In 1986 Dr. Portnoy started his independent lab at Washington University in St. Louis where he began his studies on Listeria monocytogenes. In 1988, he joined the Department of Microbiology at the University of Pennsylvania, where he collaborated with Dr. Lewis Tilney in the Biology Department and made the observation that L. monocytogenes spreads from one cell to another by exploiting a host cell system of actin polymerization. [4] His lab also defined the role of the listerial hemolysin in mediating dissolution of phagosomes. [5] In collaboration with Dr. Philip Youngman, he showed that expression of the L. monocytogenes hemolysin by Bacillus subtilis led to its growth inside of host cells. [6] Dr. Portnoy collaborated with Dr. Yvonne Paterson, who also arrived at Penn in 1988, on the use of L. monocytogenes as a recombinant vector-based vaccine for the induction of cell-mediated immunity. [7] [8] Both Drs. Paterson and Portnoy went on to work with biotech companies to develop vaccines for both cancer and infectious disease applications. [9] [10] Numerous clinical trials based on their discoveries have shown promising results as immunotherapeutic treatments for cancer.
In 1997, Dr Portnoy moved to UC Berkeley where his lab continues to examine fundamental aspects of L. monocytogenes biology, and has expanded to focus on both innate and acquired immunity in the context of Listeria infection. Dr. Portnoy and collaborators have shown that immune cells recognize cyclic di-AMP, a novel and essential bacterial signaling molecule, secreted by L. monocytogenes through multidrug resistance efflux transporters. [11] [12] Dr. Portnoy and Dr. Russell Vance identified that STING was the host receptor of cyclic-di-nucleotides (CDNs) that leads to the production of type I interferon and other co-regulated genes. [13] Modified CDNs are now being evaluated for clinical application as adjuvants and for cancer immunotherapy.
Dr. Portnoy has been awarded a number of honors over the course of his career including the Eli Lilly and Company Research Award in Microbiology & Immunology Archived 2016-05-28 at the Wayback Machine , [14] NIH Merit Award, Fellow of the American Academy of Microbiology, Senior Scholar Award in Global Infectious Diseases from the Ellison Foundation, and numerous honorary keynote lectures. In 2013, Portnoy's contributions were recognized by his election to the National Academy of Sciences. [15] In 2017, Portnoy became an Elected Fellow in the National Academy of Inventors. [16]
Dr. Portnoy has three children, Eleanor Sophie Portnoy (born 1996), Herschel Michael Portnoy (born 1999), and Anna Rose Portnoy (born 2001). His wife, Anna, is a conservation biologist. His father, Bernard Portnoy, M.D. (1929–2015) was a professor of pediatrics and infectious diseases at USC; his mother, Roslyn Portnoy (1931–2021) lived in Dana Point, CA and his sister, Deborah Brown (born 1953) lives in Sherman Oaks, CA.
Yersinia pestis is a gram-negative, non-motile, coccobacillus bacterium without spores that is related to both Yersinia enterocolitica and Yersinia pseudotuberculosis, the pathogen from which Y. pestis evolved and responsible for the Far East scarlet-like fever. It is a facultative anaerobic organism that can infect humans via the Oriental rat flea. It causes the disease plague, which caused the Plague of Justinian and the Black Death, the deadliest pandemic in recorded history. Plague takes three main forms: pneumonic, septicemic, and bubonic. Yersinia pestis is a parasite of its host, the rat flea, which is also a parasite of rats, hence Y. pestis is a hyperparasite.
Listeria monocytogenes is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host's cells and is one of the most virulent foodborne pathogens: 20 to 30% of foodborne listeriosis infections in high-risk individuals may be fatal. In the European Union, listeriosis follows an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. Listeriosis mortality rates are also higher in the EU than for other foodborne pathogens. Responsible for an estimated 1,600 illnesses and 260 deaths in the United States annually, listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even Salmonella spp. and Clostridium botulinum.
Listeria is a genus of bacteria that acts as an intracellular parasite in mammals. Until 1992, 10 species were known, each containing two subspecies. By 2024, 28 species had been identified. The genus is named in honour of the British pioneer of sterile surgery Joseph Lister. Listeria species are Gram-positive, rod-shaped, and facultatively anaerobic, and do not produce endospores. The major human pathogen in the genus Listeria is L. monocytogenes. It is usually the causative agent of the relatively rare bacterial disease listeriosis, an infection caused by eating food contaminated with the bacteria. Listeriosis can cause serious illness in pregnant women, newborns, adults with weakened immune systems and the elderly, and may cause gastroenteritis in others who have been severely infected.
Yersinia enterocolitica is a Gram-negative, rod-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29°C (72–84°F), but becomes nonmotile at normal human body temperature. Y. enterocolitica infection causes the disease yersiniosis, which is an animal-borne disease occurring in humans, as well as in a wide array of animals such as cattle, deer, pigs, and birds. Many of these animals recover from the disease and become carriers; these are potential sources of contagion despite showing no signs of disease. The bacterium infects the host by sticking to its cells using trimeric autotransporter adhesins.
Stanley "Stan" Falkow was an American microbiologist and a professor of microbiology at Georgetown University, University of Washington, and Stanford University School of Medicine. Falkow is known as the father of the field of molecular microbial pathogenesis. He formulated molecular Koch's postulates, which have guided the study of the microbial determinants of infectious diseases since the late 1980s. Falkow spent over 50 years uncovering molecular mechanisms of how bacteria cause disease and how to disarm them. Falkow also was one of the first scientists to investigate antimicrobial resistance, and presented his research extensively to scientific, government, and lay audiences explaining the spread of resistance from one organism to another, now known as horizontal gene transfer, and the implications of this phenomenon on our ability to combat infections in the future.
Shigella flexneri is a species of Gram-negative bacteria in the genus Shigella that can cause diarrhea in humans. Several different serogroups of Shigella are described; S. flexneri belongs to group B. S. flexneri infections can usually be treated with antibiotics, although some strains have become resistant. Less severe cases are not usually treated because they become more resistant in the future. Shigella are closely related to Escherichia coli, but can be differentiated from E.coli based on pathogenicity, physiology and serology.
Yersinia pseudotuberculosis is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by Y. pseudotuberculosis. The bacterium is urease positive.
Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:
Pascale Cossart is a French bacteriologist who is affiliated with the Pasteur Institute of Paris. She is the foremost authority on Listeria monocytogenes, a deadly and common food-borne pathogen responsible for encephalitis, meningitis, bacteremia, gastroenteritis, and other diseases.
Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.
Virulence-related outer membrane proteins, or outer surface proteins (Osp) in some contexts, are expressed in the outer membrane of gram-negative bacteria and are essential to bacterial survival within macrophages and for eukaryotic cell invasion.
The Actin assembly-inducing protein (ActA) is a protein encoded and used by Listeria monocytogenes to propel itself through a mammalian host cell. ActA is a bacterial surface protein comprising a membrane-spanning region. In a mammalian cell the bacterial ActA interacts with the Arp2/3 complex and actin monomers to induce actin polymerization on the bacterial surface generating an actin comet tail. The gene encoding ActA is named actA or prtB.
Paracytophagy is the cellular process whereby a cell engulfs a protrusion which extends from a neighboring cell. This protrusion may contain material which is actively transferred between the cells. The process of paracytophagy was first described as a crucial step during cell-to-cell spread of the intracellular bacterial pathogen Listeria monocytogenes, and is also commonly observed in Shigella flexneri. Paracytophagy allows these intracellular pathogens to spread directly from cell to cell, thus escaping immune detection and destruction. Studies of this process have contributed significantly to our understanding of the role of the actin cytoskeleton in eukaryotic cells.
Listeria ivanovii is a species of bacteria in the genus Listeria. The listeria are rod-shaped bacteria, do not produce spores, and become positively stained when subjected to Gram staining. Of the six bacteria species within the genus, L. ivanovii is one of the two pathogenic species. In 1955 Bulgaria, the first known isolation of this species was found from sheep. It behaves like L. monocytogenes, but is found almost exclusively in ruminants. The species is named in honor of Bulgarian microbiologist Ivan Ivanov. This species is facultatively anaerobic, which makes it possible for it to go through fermentation when there is oxygen depletion.
Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.
Cyclic di-AMP is a second messenger used in signal transduction in bacteria and archaea. It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum euryarchaeota.
Nucleomodulins are a family of bacterial proteins that enter the nucleus of eukaryotic cells.
Tumor-homing bacteria are facultative or obligate anaerobic bacteria that are able to target cancerous cells in the body, suppress tumor growth and survive in the body for a long time even after the infection. When this type of bacteria is administered into the body, it migrates to the cancerous tissues and starts to grow, and then deploys distinct mechanisms to destroy solid tumors. Each bacteria species uses a different process to eliminate the tumor. Some common tumor homing bacteria include Salmonella, Clostridium, Bifidobacterium, Listeria, and Streptococcus. The earliest research of this type of bacteria was highlighted in 1813 when scientists began observing that patients that had gas gangrene, an infection caused by the bacteria Clostridium, were able to have tumor regressions.
Virginia L. Miller is a microbiologist known for her work on studying the factors leading to disease caused by bacteria. Miller is an elected fellow of the American Academy of Microbiology (2003) and a former Pew Charitable Trust Biomedical Scholar (1989).
Mary X. D. O’Riordan is an American molecular biologist who is the Frederick C. Neidhardt Collegiate Professor of Microbiology and Immunology at the University of Michigan. She also serves as Dean for Graduate and Postdoctoral Studies at Michigan Medicine.