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Academic Background

B.S.   (1975)  University of Michigan

M.D.  (1980)   University of Michigan

Internship and Residency, Internal Medicine (1980-1983) 

                         George Washington University Hospital

Infectious Diseases Fellowship (1984-1986)

             University of Wisconsin Hospitals and Clinics

Post-doctoral Fellowship (1986-1988)

             University of Wisconsin Hospitals and Clinics

             (Christian R.H. Raetz, mentor)

Post-doctoral Fellowship (1989-1990)

             Merck Research Laboratories, Rahway, NJ

             (Christian R.H. Raetz, mentor)

Assistant Professor of Medicine and Infectious Diseases (1990- 1995)

             Boston University School of Medicine

Associate Professor of Medicine and Infectious Diseases (1995-1999)

             Boston University School of Medicine

Professor of Medicine and Infectious Diseases (1999-2001)

             Boston University School of Medicine

Professor of Medicine and Infectious Diseases (2001-present)

              UMass Medical School

             Tenure award:  2004

           

Innate immunity and Infectious Diseases.Douglas Golenbock, MD

Dr. Douglas Golenbock is Chief of the Division of Infectious Diseases and Immunology in the Department of Medicine. He holds a joint appointment in the Department of Microbiology and Physiological Systems. The goal of his laboratory is to characterize phagocytic receptors that recognize the presence of microbes in the context of infectious illnesses. As the mechanisms of inflammation in infectious diseases are similar to those associated with sterile inflammation, we also study Alzheimer's Disease.    Virtually all of our work focuses on two groups of receptors: Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in the context of the inflammasome.

 Our entry into the TLR field was heralded by the discovery that TLR4, and MD-2 mediate responses to bacterial endotoxin, a major cause of sepsis. More recently, we have begun to focus on intracellular nucleic acid receptors as regulators of IL-1 production and type I interferons. There are six major projects in the laboratory:

1. Defining the response to bacterial lipopolysaccharide (LPS, endotoxin). LPS immunologically potent amphipathic glycolipid on the surface of Gram-negative bacteria. It is thought to be responsible for Gram-negative sepsis. This project involves detailed studies of TLR4/MD-2 and adapter molecules that transduce an activation signal. The work is funded via an NIH merit award to Dr. Golenbock.

2. Characterizing the role of the LPS receptor system, in pelvic inflammatory disease. This project is based upon the realization that Neisseria gonorrhoeae mediates much of its inflammation via the TLR4/MD-2 signaling pathway and is funded via an NIH U19 award that includes other infectious diseases faculty, including Drs. Peter Rice (program PI) and Sanjay Ram.

3. Defining the innate immune response to P. falciparum malaria. Very little is known about how P. falciparum causes inflammation. We have developed several projects in this area, including basic investigations into nucleic acid receptors and inflammasomes. This is a large project that is a collaboration with two other UMass investigators, Drs. Kate Fitzgerald and Ricardo Gazzinelli. The project is funded via an RO1 to Drs. Golenbock and Fitzgerald.

4. Defining the innate immune response to Group B streptococcus. We have previously demonstrated that Group B streptococcus activates type I interferon production as a result of hemolysin expression, which allows DNA access to the phagocyte cytosolic compartment. Recent studies also implicate hemolysin as a mediator of NLRP3 activation via the effects of bacterial RNA. This project is a three way collaboration with a bacterial genetics group at the Institut Pasteur (France) headed by Dr. Patrick Trieu-Cuot and a cell biology group at the University of Freiburg (Germany) run by Dr. Philipp Henneke, a former Golenbock post-doctoral fellow, and is funded by an RO1 grant to Dr. Golenbock.

5. Defining a role for PSTPIP1. PSTPIP1 is a protein that causes an autoinflammatory disorder known as PAPA syndrome: Pogenic Arthritis, Pyoderma gangrenosum and Acne. The disease is due to dysregulation of IL-1 production that probably results from the activation on pyrin, the gene product associated with Familial Mediterranean Fever. Dr. Donghai Wang, a member of the Golenbock laboratory, has engineered mice that are either deficient in PSTPIP1, or that carry the known lesions of PAPA syndrome. It is funded by an R21 grant to Drs. Wang and Golenbock.

6. Examining the role of the NLRP3 inflammasome in Alzheimers Disease. Alzheimer (AD) is a chronic inflammatory disease that causes premature dementia and death. It appears to be caused, in part, by -amyloid, an insoluble protein that activates the NLRP3 inflammasome in microglial cells, resulting in neuronal cell death.

One of the major goals of the Golenbock lab and the Division of Infectious Diseases is to promote UMass immunology and the field of innate immunity in general. The Division has organized the state of the art meetng in the field of innate immunity. We have now had four Toll meetings: Toll2004 (Taormina, Italy), Toll2006 (Salvador, Brazil; www.toll2006.org), Toll2008 (Cascais, Portugal; www.toll2008.org) and Toll2011 (Riva del Garda, Italy; www.toll2011.org). Virtually all of the research faculty, students and post-docs in Infectious Diseases attend the Toll meetings, which typically involve ~ 600 participants.

For More information on Toll related meetings please see

 http://www.youtube.com/watch?v=2rqQOmkiL5o

For More information on Targeting a new therapy for Alzheimer's pleas see:

 http://www.youtube.com/watch?v=5LXshrNFkXA

 


One or more keywords matched the following items that are connected to Golenbock, Douglas

Item TypeName
Academic Article Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system.
Academic Article Engagement of the Lewis X antigen (CD15) results in monocyte activation.
Academic Article Effects of interleukin-10 on human peripheral blood mononuclear cell responses to Cryptococcus neoformans, Candida albicans, and lipopolysaccharide.
Academic Article Helicobacter pylori lipopolysaccharide binds to CD14 and stimulates release of interleukin-8, epithelial neutrophil-activating peptide 78, and monocyte chemotactic protein 1 by human monocytes.
Academic Article Structure and function of Toll-like receptor proteins.
Academic Article Stimulation of macrophages by lipopolysaccharide alters the phosphorylation state, conformation, and function of PU.1 via activation of casein kinase II.
Academic Article Characterization of proinflammatory cytokine production and CD14 expression by murine alveolar macrophage cell lines.
Academic Article Lipopolysaccharides from periodontopathic bacteria Porphyromonas gingivalis and Capnocytophaga ochracea are antagonists for human toll-like receptor 4.
Academic Article Construction of a lipopolysaccharide reporter cell line and its use in identifying mutants defective in endotoxin, but not TNF-alpha, signal transduction.
Academic Article Neutrophil influx in response to a peritoneal infection with Salmonella is delayed in lipopolysaccharide-binding protein or CD14-deficient mice.
Academic Article Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells.
Academic Article The LPS receptor generates inflammatory signals from the cell surface.
Academic Article Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response.
Academic Article Use of a photoactivatable taxol analogue to identify unique cellular targets in murine macrophages: identification of murine CD18 as a major taxol-binding protein and a role for Mac-1 in taxol-induced gene expression.
Academic Article Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi.
Academic Article Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling.
Academic Article Human toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide.
Academic Article Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling.
Academic Article Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM.
Academic Article Immunology. The shape of things to come.
Academic Article Identification of a key pathway required for the sterile inflammatory response triggered by dying cells.
Academic Article YopJ targets TRAF proteins to inhibit TLR-mediated NF-kappaB, MAPK and IRF3 signal transduction.
Academic Article Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite.
Academic Article Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling.
Academic Article Bacterial fimbriae stimulate proinflammatory activation in the endothelium through distinct TLRs.
Academic Article Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function.
Academic Article A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling.
Academic Article Mal connects TLR2 to PI3Kinase activation and phagocyte polarization.
Academic Article MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3.
Academic Article Novel engagement of CD14 and multiple toll-like receptors by group B streptococci.
Academic Article Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation.
Academic Article Activation of the NLRP3 inflammasome by group B streptococci.
Academic Article Involvement of toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers.
Academic Article NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice.
Academic Article CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation.
Academic Article The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism.
Academic Article Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is Toll-like receptor 2 dependent.
Academic Article Innate immune responses to Rhodococcus equi.
Academic Article Stimulation of toll-like receptor 2 by Coxiella burnetii is required for macrophage production of pro-inflammatory cytokines and resistance to infection.
Academic Article Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling.
Academic Article HMGB1 signals through toll-like receptor (TLR) 4 and TLR2.
Academic Article MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals.
Academic Article Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition.
Academic Article NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1.
Academic Article Plasmodium falciparum infection causes proinflammatory priming of human TLR responses.
Academic Article Failure of TLR4-driven NF-kappa B activation to stimulate virus replication in models of HIV type 1 activation.
Academic Article IL-10 enhances MD-2 and CD14 expression in monocytes and the proteins are increased and correlated in HIV-infected patients.
Academic Article MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses.
Academic Article Inflammasomes: too big to miss.
Academic Article Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule.
Academic Article UNC93B1 mediates host resistance to infection with Toxoplasma gondii.
Academic Article TLR3-mediated IFN-ß gene induction is negatively regulated by the TLR adaptor MyD88 adaptor-like.
Academic Article Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi.
Academic Article NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1ß and neuronal toxicity.
Academic Article Defective pro-IL-1ß responses in macrophages from aged mice.
Academic Article Inflammation in mice ectopically expressing human Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome-associated PSTPIP1 A230T mutant proteins.
Academic Article UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major.
Academic Article Interferon-? and granulocyte/monocyte colony-stimulating factor production by natural killer cells involves different signaling pathways and the adaptor stimulator of interferon genes (STING).
Academic Article SDZ MRL 953, a lipid A analog as selective cytokine inducer.
Concept Interleukin-10
Concept Receptors, Interleukin-1
Concept Interleukin-1alpha
Concept Interleukin-15
Concept Receptors, Interleukin-2
Concept Interleukin-1 Receptor-Associated Kinases
Concept Interleukin-18 Receptor alpha Subunit
Concept Interleukin-1
Concept Interleukin 1 Receptor Antagonist Protein
Concept Interleukin-1beta
Concept Interleukin-8
Concept Interleukin-12 Subunit p40
Concept Interleukin-4
Concept Interleukin-6
Concept Receptors, Interleukin
Concept Interleukin-18
Concept Interleukin-12
Concept Receptors, Interleukin-18
Academic Article Dual engagement of the NLRP3 and AIM2 inflammasomes by plasmodium-derived hemozoin and DNA during malaria.
Academic Article Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.
Academic Article TRIF signaling is essential for TLR4-driven IgE class switching.
Academic Article 3-Hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin)-induced 28-kDa interleukin-1ß interferes with mature IL-1ß signaling.
Academic Article RNA and ß-hemolysin of group B Streptococcus induce interleukin-1ß (IL-1ß) by activating NLRP3 inflammasomes in mouse macrophages.
Academic Article Hemolysis-induced lethality involves inflammasome activation by heme.
Academic Article Metalloproteinase-dependent TLR2 ectodomain shedding is involved in soluble toll-like receptor 2 (sTLR2) production.
Academic Article A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling.
Academic Article Activation of the NLRP3 inflammasome in microglia: the role of ceramide.

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