Free

Advances in Gene Therapy

Event Information

Share this event

Date and Time

Location

Location

CIC Boston

50 Milk St

Boston, MA

View Map

Friends Who Are Going
Event description

Description


Join us for a presentation and discussion on advances in gene therapy with two Boston scientists. Dr. Neena Haider is an expert in genetics and retinal disease. Dr. Parmit Kumar Singh is presenting his research: HIV-1, cancer and splicing: the triangle.
6:00PM Meet & Greet
6:30PM Presentations

Presenters:

Neena B. Haider, PhD
Harvard Medical School: Associate Professor of Ophthalmology
The focus of Dr. Haider’s research is to elucidate the underlying mechanisms associated with inherited retinal disorders and develop novel, effective therapies to treat retinal degenerations. Dr. Haider’s efforts have led to the identification of over a dozen genes and mutations associated with human retinal disease. Her lab has determined key genetic factors influencing the disease state in syndromic and non-syndromic retinitis pigmentosa (RP), age related macular degeneration (AMD), and diabetic retinopathy (DR). Her work has uncovered the role of nuclear hormone receptor genes in modulating the normal and diseased state in the retina. She discovered role of Nr2e3 in proper photoreceptor development, function, and retinal degeneration. Her lab also helped uncover the role of RORA, antioxidants, and vitamin D metabolism in AMD.

Dr. Haider’s lab combines unique expertise in human genetics, functional genomics and mouse genetics. Her lab has procured and developed over 30 strains of mouse models for RP, DR, and AMD. Her work has uncovered key pathways and gene networks important for retinal development and function. The lab recently demonstrated multimodal regulation by miRNA, nuclear hormone receptors, and epigenetic factors in the retina. Her continued work on genetic modifier genes has led to key discoveries of potent nuclear hormone receptors that can rescue retinal disease in early and intermediate states and reset a homeostatic state in the diseased retina. Dr. Haider’s work is highly translational and has broad therapeutic impacts. Dr. Haider’s work has been cited in over 1000 publications and is internationally recognized in the fields of human genetics, retinal development and disease, gene and cell therapies, and nuclear hormone receptors. She serves on several grant review panels for NIH and National Science Foundation in neuroscience and vision and was appointed as a standing member to NIH-NEI’s BVS panel.


Parmit Kumar Singh, PhD
Scientist I DFCI, Harvard

HIV-1, cancer and splicing: the triangle

HIV-1 prefers integration in actively transcribed genes. This bias preference for integration into genes depends on the interaction between HIV-1 integrase and the host chromatin-binding factor LEDGF/p75. LEDGF/p75 is a transcription factor, and it has a chromatin binding PWWP domain and an integrase-binding domain. However, the cellular role of LEDGF/p75 is not well understood. It is also not known how LEDGF/p75 recognizes actively transcribed genes. Further, it is unknown whether HIV-1 has any preference for specific kind of genes like cancer genes or HIV-1 targets all genes equally.

HIV-1 based vectors are popular in gene therapy to avoid oncogene activation by gamma retrovirus based vectors in gene therapy recipients. However, there is not much information about whether HIV-1 shows preference for cancer genes. Therefore, to understand the mechanism of LEDGF/p75-dependent integration, I determined 1 million unique integration sites of HIV-1 in human cultured cells by pair-end Illumina sequencing.

Bioinformatic analysis of these integration sites showed that HIV-1 prefers integration into cancer genes were preferentially targeted. My result is significant as it stresses for further study to design a safe HIV-1 based vector for gene therapy by considering the associated risk.

Further, I developed new methods to do bioinformatics analysis of these one million integration sites. By this new method I found that HIV-1 prefers integration into genes with more number of introns or highly spliced genes. Also, I showed that the preference for integration into highly spliced genes depends on LEDGF/p75. This was a very significant result as it not only suggests the cellular role of LEDGF/p75 in splicing but also it suggests a link between the normal cellular process splicing, HIV-1 integration and cancer as it is known that misregulation of splicing causes many disease like cancer. Further studies to understand the mechanism of splicing and its role in HIV-1 integration are needed to develop a better picture

Speaker Bio
Dr. Parmit Kumar Singh completed his PhD at Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India. Dr. Singh determined the threshold size of duplicated DNA that titrates repeat induced point mutation (RIP) machinery. Moreover, He identified the first wild-isolate strain of Neurospora as a dominant suppressor of meiotic silencing. Both RIP and meiotic silencing are genome defense process in Neurospora.

During his postdoc at National Institutes of Health, he researched the integration preference of HIV-1 and his results, based on one million integration sites of HIV-1 in human cultured cells, showed that HIV-1 has preference for the highly spliced and cancer genes. The result was published in Genes and Development.
He is going to share his results about HIV-1 preference for highly spliced genes.

Dr. Singh has also taught at the Foundation for Advanced Education in the Science (FAES), and Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USA.

Share with friends

Date and Time

Location

CIC Boston

50 Milk St

Boston, MA

View Map

Save This Event

Event Saved