PCMM | Highlights

  June 15, 2017

Jun (Jacob) Hu was awarded Cancer Research Institute Irvington Post-doctoral Fellowship

junhuCongratulations to Dr. Jun Hu, who has each been awarded a post-doctoral fellowship from the Cancer Research Institute (CRI).

Jun Jacob Hu, a postdoctoral fellow in the Hao Wu lab, will use high-throughput screening, biochemical characterization and structural studies to identify potential inhibitors against Gasdermin D (GSDMD). Gasdermin D is a recently identified downstream effector of inflammasomes. This project will provide significant insight into the regulation mechanism of the pore-forming activity of GSDMD in pyroptotic cell death and may lead to new therapeutic strategies for disease treatment.

 May 1, 2017

Yang Li was awarded Career Development Fellowship by Boston Children's Hospital

NLRP3 inflammasome is a multiprotein assembly responsible for activation of inflammatory process through the recognition of a broad spectrum of signals. Autosomal dominant mutations in the NLRP3 expressing gene are associated with auto-inflammatory diseases, named cryopyrin-associated syndrome (CAPS). Sterile inflammation by NLRP3 has been shown to contribute to other human diseases that include gout, cardiovascular diseases and Alzheimer’s disease. During this 2-year award Dr. Li, an Instructor in Hao Wu's laboratory,  will investigate the auto-inhibition and activation mechanism of NLRP3. He will also elucidate the interactions between caspase recruitment domains (CARDs) of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, which mediate NLRP3 inflammasome formation. Dr. Li also aims to identify small molecule inhibitors that are capable of interfering with the inflammasome assembly.

 April 12, 2017

Tianmin Fu Received Harvard Digestive Diseases Center Pilot Feasibility Grant

NLRP6 inflammasome plays vital roles in host defense at the intestinal epithelium and in maintaining the gut microbiota ecosystem. Tianmin Fu, an Instructor in Hao Wu's laboratory will employ multi-disciplinary biochemical and biophysical methods to understand the molecular mechanism of the NLRP6 inflammasome assembly and activation. These study could contribute to the understanding and treatment of many digestive diseases such as inflammatory bowel diseases and colorectal cancer.

July 7, 2016

When antibiotics fail: A potential new angle on severe bacterial infection and sepsis

By Nancy Fliesler

Bacterial infections that don’t respond to antibiotics are of rising concern. And so is sepsis — the immune system’s last-ditch, failed attack on infection that ends up being lethal itself. Sepsis is the largest killer of newborns and children worldwide and, in the U.S. alone, kills a quarter of a million people each year. Like antibiotic-resistant infections, it has no good treatment.

Reporting this week in Nature, scientists in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM) describe new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.

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 June 1, 2016

Congratulations to Alvin Lu, a graduate student in the Wu Lab.

Congratulations to Alvin Lu, a graduate student in the Wu lab for a successful defense of his thesis entitled "Assembly and Regulation of the Inflammasome Governed by a Unified Polymerization Mechanism".

 January 5, 2016

Dr. Liman Zhang was awarded the Cancer Research Institute Irvington Postdoctoral Fellowship

Dr. Zhang, a postdoctoral fellow in the Wu lab will investigate the structure and regulation mechanism of inflammasome complexes, which are defenders against cytosolic infections by pathogen through recruitment and activation of pro-caspase-1. Abnormal inhibition and activation of the inflammasome 

complexes cause many human diseases. For example in the NAIP/NLRC4 inflammasome complex, NLRC4 knockout mice show increased tumor formation compared with wild type mice. NLRC4, along with caspase-1, has been shown to regulate tumorigenesis in a mouse model of colitis-associated colorectal cancer (CAC). This work will provide important insights into cytosolic pathogen sensing mechanisms that could lead to new strategies on disease treatment and drug development.

December 14, 2015

Putting Structure Around the Genetic Basis of Some Immune Diseases

The saying in the design world is that form follows function. But in biology, and protein biology in particular, it would be more correct to say that form begets function. Shape and structure are the foundation for most protein-based interactions in cells, and are why basic functions like receptor binding, antibody neutralization and gene transcription work.

Two enzymes in the immune system’s B cells, called RAG1 and RAG2, are a perfect example. Together, they form a complex that splices antibody-producing genes together in unique combinations through a process called V(D)J recombination. They do a similar job in T cells to build antigen-binding T-cell receptors (TCRs). In either case, the enzymes are essential to a robust immune response.

In a recent Cell paper, a team led by Hao Wu, PhD, of the Program in Cellular and Molecular Medicine (PCMM) at Boston Children’s Hospital and Maofu Liao, PhD, at Harvard Medical School used electronic microscopy to reveal how RAG1 and 2 interact at a structural level, both with each other and with DNA. The structural biology images they’ve created show plainly what mutations in the genes for these proteins do to cause disease.

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October 22, 2015

Hao Wu was awarded the NIH Director's Pioneer Award

HaoWu_2Congratulations to Professor Hao Wu for being awarded the NIH Director's Pioneer Award.The NIH Pioneer Awards program support exceptional investigators pursuing bold research projects that span the broad mission of the NIH, including developing methods for cells to synthesize their own drugs, using cell phones to identify and track disease-carrying mosquitoes in their natural habitats, stopping depression by monitoring and altering brain cell states, and exploring how socially learned behavior can be passed on biologically to future generations. This year Hao Wu is one of 13 recipients of the the NIH Director's Pioneer Award. 

Hao Wu received her pre-medical training at Peking University from 1982 to 1985 and studied Medicine at Peking Union Medical College from 1985 to 1988. She obtained her Ph.D. degree in Biochemistry from Purdue University in 1992, working in the laboratory of Professor Michael Rossmann. After performing postdoctoral training at Columbia University in the laboratory of Professor Wayne Hendrickson, she became an Assistant Professor at Weill Cornell Medical College in 1997 and was promoted to Professor in 2003. In 2012, Hao moved to Harvard Medical School as the Asa and Patricia Springer Professor of Biological Chemistry and Molecular Pharmacology, and as the Senior Investigator in the Program in Cellular and Molecular Medicine of Boston Children’s Hospital. Hao has received a number of honors, including the Howard Hughes Medical Institute pre-doctoral fellowship, the Aaron Diamond postdoctoral fellowship, the Pew Scholar award, the Rita Allen Scholar award, New York Mayor’s Award for Excellence in Science and Technology, the Margaret Dayhoff Memorial Award from the Biophysical Society, and Purdue University Distinguished Science Alumni Award. She serves on the Scientific Advisory Council of the Cancer Research Institute and the Editorial Board of Cancer Cell. She is an elected member of the National Academy of Sciences.   

 April 28, 2015

Congratulations to Professor Hao Wu for being elected to the National Academy of Sciences

The National Academy of Sciences (NAS) announced their election of 84 new members and 21 foreign associates in recognition of their distinguished achievements in original research. Among these new members is Dr. Hao Wu, Asa and Patricia Springer Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School, and Senior Investigator in the Program in Cellular and Molecular Medicine at Boston Children's Hospital.