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Alt Lab Highlights



 September 8, 2016  

Keeping up with HIV mutations: Building a nimble vaccine test system

An AIDS vaccine able to fight any HIV strain has thus far eluded science. HIV frequently mutates its coat protein, dodging vaccine makers’ efforts to elicit sufficiently broadly neutralizing antibodies.

Yet sometimes HIV-infected people can produce such antibodies on their own. This usually requires years of exposure to the virus, allowing the immune system to modify its antibodies over time to keep up with HIV mutations. But the goal is generally achieved too late in the game to prevent them from being infected.

“Only a small fraction of patients are able to develop broadly neutralizing antibodies, and by the time they do, the virus has already integrated into the genomes of their T-cells,” says Ming Tian, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM).

Tian is part of a group led by PCCM director Frederick Alt, PhD, that developed a technology to greatly speed up HIV development. Described today in Cell, the group’s method generates mouse models with built-in human immune systems. The model recapitulates what the human immune system does, only much more rapidly, enabling researchers to continuously test and tweak potential HIV vaccines.

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 August 26, 2016

Pei-Chi Wei was awarded Charles A. King Trust Postdoctoral Fellowships

Dr. Wei (right) a postdoctoral fellow in the Alt lab has previously identified classes of recurrent DNA double strand breaks (RDC) that occurred frequently in the body of long genes in murine neural stem and progenitor cells (NSPCs).  These genes have been implicated in neuropsychiatric diseases and many are rearranged in cancers, including brain cancers.   Dr. Wei aims to elucidate the roles of RDCs in NSPCs in neuronal cell diversification and brain diseases development.Dr. Wei a postdoctoral fellow in the Alt lab has previously identified classes of recurrent DNA double strand breaks (RDC).


 

July 14, 2016

Dr. Cheng-Sheng Lee was awarded the Cancer Research Institute Irvington Postdoctoral Fellowship

During this fellowship Dr. Lee will investigate how recombination activating gene endonuclease (RAG) mediates recombination between bona fide RAG recognition sequences (RRSs). Specifically, Dr. Lee will examine the mechanism of RAG tracking, a model originally proposed to explain the RAG off-target joining happened exclusively between convergent RSSs in topologically associated domains. He will also investigate driving forces that propel RAG tracking through a chromosomal loop. The proposed work will help provide fundamental understanding of normal antibody repertoire development and mechanisms of chromosomal translocations in lymphoid cancers. 


 May 26, 2016

Congratulations to Rohit Panchakshari

Congratulations to Rohit Panchakshari, a graduate student in the Alt lab for a successful defense of his Ph.D. thesis entitled "Investigating Mechanisms of DNA Double Strand Break joining of Switch regions during IgH Class Switch Recombination".



 March 2, 2016

Dr. Huan Chen Received Career Development Fellowship from the Leukemia & Lymphoma Society

During this fellowship Dr. Chen, a postdoctoral fellow in the laboratory of Dr. Fred Alt, will elucidate the mechanistic components and physiologic function of alternative end joining (A-EJ), a DNA double-strand break (DSB) repair pathway that likely contributes to lymphoid and other tumors. She will study A-EJ in the context of IgH class switch recombination (CSR) using a newly developed high throughput genome wide translocation sequencing (HTGTS)-based assay.  Fully characterizing A-EJ will help to understand the onset and progression of some blood cancers and reveal novel targets for cancer treatment.


 February 25, 2016

Fred Alt received Willian Silen Lifetime Achievement in Mentoring Award from Harvard Medical School

Dr. Frederick W. Alt received William Silen Lifetime Achievement in Mentoring Award from Harvard Medical School in recognition of Dr. Alt's impact on professional development and career advancement in research.


 

February 11, 2016

Adopted from Boston Children's Hospital News Release

DNA breaks in nerve cells' ancestors cluster in specific genes

Study reveals new avenue for thinking about brain development, brain tumors and neurodevelopmental/psychiatric diseases

By Tom Ulrich

The genome of developing brain cells harbors 27 clusters, or hotspots, where its DNA is much more likely to break in some places than others, according to research from Harvard Medical School and Boston Children’s Hospital.

Those hotspots appear in genes associated with brain tumors and a number of neurodevelopmental and neuropsychiatric conditions.

The findings, reported Feb. 11 in Cell, raise new questions about the origins of these conditions as well as how the brain generates a diversity of circuitry during development.

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 January 5, 2016

Dr. Zhaoqing Ba was awarded the Cancer Research Institute Irvington Postdoctoral Fellowship

Dr. Ba, a postdoctoral fellow in the Alt lab, will investigate the mechanisms that mediate the intra-locus and inter-locus regulation of V(D)J recombination at Ig kappa and Ig lambda loci during B cell development, and identify RAG off-target activities genome-wide. This work will provide new insights into mechanisms of chromosomal translocations associated with leukemias and lymphomas and ultimately could provide insights into minimizing or preventing such aberrant events.



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