Speakers

Abstract:
To engineer tissue-like structures, cells must organize themselves into three-dimensional networks that mimic the native tissue microarchitecture. Microfabricated hydrogel substrates provide a potentially useful platform for directing cells into biomimetic tissue architecture in vitro. Here, some microscale technologies will be introduced to build muscle-like fibrous structures in a facile and highly reproducible fashion. The use of carbon-based nanomaterials (i.e., carbon nanotubes and graphene) to enhance electrical and mechanical properties of hydrogel-based scaffolds will be discussed. Interestingly, anisotropic electrical conductivity of scaffolds was achieved by which the maturation of skeletal muscle tissues was enhanced by the aid of electrical stimulation. In the second part of talk, I will present the fabrication of an elastomeric and shape-memory scaffold to be used for minimally invasive delivery of functional tissues. The function of engineered tissues will be preserved after the injection through small tubes in vitro and after the delivery into small and large animals. These scaffolds may find wide applications for clinical translation of engineered tissues.

Biography:
Dr. Samad Ahadian is a development engineer at the C-MIT (Khademhosseini’s Lab.) as well as Department of Bioengineering, UCLA. He has done extensive research on skeletal muscle tissue engineering, cardiac tissue regeneration, nanobiomaterials, hydrogels, and antimicrobial materials. His research works have been published in top-tier journals, including Nature Materials, Advanced Materials, Nano Letters, Lab on a Chip, and Nanoscale. He received his PhD in materials science from Tohoku University (Japan) in 2011. He worked as postdoctoral research associate and then assistant professor at Tohoku University until 2015. Following that, he held positions as a research fellow at University of Toronto (Canada) and then as a Biomaterials Scientist at the Covalon Technologies Ltd., Canada.

Abstract:
The classic methods for mapping a disease-associated gene fall into two main categories: association study and linkage analysis. Both approaches can be used for studying rare variants; however, association studies of rare variants require a large number of cases and controls, making this approach economically unattractive. Linkage analysis has been successfully used for determining many of the already identified cancer-associated genes. A classic (parametric) linkage analysis is based on the co-segregation of genetic markers with a disease in large families with multiple individuals affected over several generations. In this method, a collection of the genome-wide distributed genetic markers is genotyped among affected individuals in a family, and one or several markers showing linkage with the studied phenotype are further investigated in additional affected and unaffected family members to confirm their co-segregation with the phenotype. The genetic marker showing co-segregation with the phenotype is believed to be in genetic linkage with the causative allele. In the search for human disorder susceptibility genes, homogeneous populations resemble a large extended family. However, because the genetic linkage blocks are expected to be much smaller in a larger homogenous population compared to a single family, a much larger number of genetic markers should be used in this setting. This makes the use of commonly used genetic markers for linkage studies very difficult and even impractical for studying unrelated individuals in a homogeneous population. This problem could be resolved by studying the causative allele directly rather than using genetic markers based on the genetic linkage concept. The availability of relatively inexpensive and highly parallel DNA sequencing methods makes it possible to study the causative allele directly rather than using genetic markers as an indirect tool.

Biography:
Dr. Akbari is an assistant professor at the Dalla Lana School of Public Health, University of Toronto (U of T), and a scientist at Women’s College Research Institute (WCRI), Women’s College Hospital (WCH). He is also an adjunct faculty member at Institute of Medical Science, faculty of Medicine, University of Toronto and the director of the Molecular Genetics Laboratory at Women's College Hospital. Dr. Akbari's research interest is in studying genetic susceptibility to cancers, including breast, ovarian, esophageal, Colon, pancreas and prostate cancers. This includes identifying new genes responsible for hereditary cancers, defining the role of known cancer genes, and individualizing cancer treatments for patients carrying a genetic mutation. One of the key focuses of his research program is to incorporate our current knowledge of cancer genetics into population strategies for reducing cancer burden by improving the current models of offering genetic screening for hereditary cancers. Dr. Akbari has published over 120 peer-reviewed papers in his relatively short career; some of them are in prestigious journals such as Nature Genetics, Journal of National cancer Institute (JNCI) and JAMA Oncology. Among them is the identification of a new breast cancer susceptibility gene named RECQL published in 2015 in Nature Genetics Journal.

Abstract:
Finally approved in 2017, it seems that CAR T cell therapy could be one of the most promising cancer therapy to treat refractory cases, but unfortunately, solid tumors have more sophisticated story. Lack of a suitable tumor specific antigen, poor tumor infiltration and the immunosuppressive tumor microenvironment (TME) altogether hinder the successful CAR T therapy in solid tumor. We designated two approaches to improve the CAR therapy in ovarian malignancies. TGFb is a pleiotropic cytokine, which induces or promotes metastasis and neoangiogenesis and potently suppresses the immune system. Here we used the novel gene editing machinery, CRISPR/Cas9, to knockout the TGFb receptor gene in CAR T cells and prove that KO-CAR T cells could resist the inhibitory effect of TGFb in vitro. On a parallel project, we worked on a new designation of CAR construct, namely TCR-CAR, and could prove that this construct is functional in vitro in terms of proliferation, cytotoxicity and cytokine secretion and could outperform classical CAR T cells in low doses of antigen presenting. These data can be a promising opportunity in solid tumor immunotherapy.

Abstract:
TBA

Biography:
NGhasem Hosseini Salekdeh in a Professor in Systems Biology at ‘Royan Institute for Stem Cell Biology and Technology’ and ‘Agricultural Biotechnology Research Institute of Iran’. He is also Honorary Professor of Macquarie University, Australia. He is involved in several large-scale collaborative international including the Chromosome-Centric Human Proteome Project (C-HPP), a project organized by the Human Proteome Organization (HUPO). He serves as Chair of Human Y Chromosome Proteome Project (Y-HPP). He is also chair of the Asia Oceania Human Proteome Organization (AOHUPO) project on Human Embryonic Stem Cell Membrane since 2014. He is actively involved in national and international scientific societies. He is Co-founder of Iranian Proteomics Society (2004) and president of the society from 2004 till 2014. He is also an active council member of Asia Oceania Human Proteome Organization (AOHUPO) (2004 – present). He is on the editorial board of several leading journals in the field such as Nature Scientific Reports, Journal of Proteome Research, and Proteomics. He has published about 160 scientific papers with >11400 citations, h index 43 (Google scholar). He has published papers in the fields of proteomics and systems biology in top tier journals including Nature Biotechnology, Journal of Hepatology, Nature protocols, Trends in Plant Science, Nucleic Acids Research, Autophagy, Pharmacology & Therapeutics, Molecular Plant, Stem Cell reports, Molecular Therapy, Molecular and Cellular Proteomics, and Journal of Proteome Research. He has been recognized as “top 1% of world scientists” in Biochemistry and Molecular Biology based on Thomson Reuters (ISI) reports (Oct 2015).

Abstract:
TBA

Biography:
Ghasem Hosseini Salekdeh in a Professor in Systems Biology at ‘Royan Institute for Stem Cell Biology and Technology’ and ‘Agricultural Biotechnology Research Institute of Iran’. He is also Honorary Professor of Macquarie University, Australia. He is involved in several large-scale collaborative international including the Chromosome-Centric Human Proteome Project (C-HPP), a project organized by the Human Proteome Organization (HUPO). He serves as Chair of Human Y Chromosome Proteome Project (Y-HPP). He is also chair of the Asia Oceania Human Proteome Organization (AOHUPO) project on Human Embryonic Stem Cell Membrane since 2014. He is actively involved in national and international scientific societies. He is Co-founder of Iranian Proteomics Society (2004) and president of the society from 2004 till 2014. He is also an active council member of Asia Oceania Human Proteome Organization (AOHUPO) (2004 – present). He is on the editorial board of several leading journals in the field such as Nature Scientific Reports, Journal of Proteome Research, and Proteomics. He has published about 160 scientific papers with >11400 citations, h index 43 (Google scholar). He has published papers in the fields of proteomics and systems biology in top tier journals including Nature Biotechnology, Journal of Hepatology, Nature protocols, Trends in Plant Science, Nucleic Acids Research, Autophagy, Pharmacology & Therapeutics, Molecular Plant, Stem Cell reports, Molecular Therapy, Molecular and Cellular Proteomics, and Journal of Proteome Research. He has been recognized as “top 1% of world scientists” in Biochemistry and Molecular Biology based on Thomson Reuters (ISI) reports (Oct 2015).

Abstract:
Acute myeloid leukemia (AML) is composed of functionally heterogeneous cells including leukemic stem cells (LSCs), which exhibit the ability to self-renew and propagate disease. It is thought that failure of common chemotherapy regimens is due to insufficient eradication of LSCs. However, the mechanisms that maintain stem cell function in the hematopoietic system are not well understood. MicroRNAs play an important role in the regulation of normal and malignant hematopoietic stem cells. Our studies showed that miR-99, a miRNA highly expressed in AML patient cell populations enriched for LSC activity, is among the most highly expressed miRNAs in hematopoietic stem cells (HSCs), suggesting that miR-99 plays a role in regulating normal HSCs as well as LSCs. To test the role of miR-99 in normal hematopoiesis, we knocked down (KD) miR-99 in mouse HSCs (Lin-cKit+Sca1+CD34-SLAM+), which resulted in ~3 fold reduced methylcellulose colony formation upon secondary plating (P=0.01), as well as accelerated granulopoiesis as demonstrated by increased Gr1+Mac1+ cells 7 days after culture initiation (P<0.01), suggesting that miR-99 functions to suppresses differentiation. Consistent with this model, transplantation assays demonstrated >10-fold reduction in long-term engraftment capacity of miR-99 KD compared to scrambled controls (P=0.0004). In addition, Ki-67/DAPI staining of stably engrafted miR-99 KD hematopoietic stem and progenitor cells (HSPCs) showed increased cell cycling, demonstrating that miR-99 also maintains HSPC quiescence. Gene set enrichment analysis (GSEA) of RNA-sequencing data generated from stably engrafted Lin-Sca-1+cKit+ cells revealed that miR-99 KD induces significant depletion of LT-HSC gene signatures (P<0.001) and induction of a late progenitor signature (P < 0.001), providing further evidence that miR-99 normally functions to maintain HSPCs in the undifferentiated state. To test whether miR-99 maintains LSCs, we performed miR-99 KD experiments using the MLL-AF9 retroviral mouse model. miR-99 KD resulted in a significant extension in survival in secondary transplants compared to scrambled controls (median 92 days vs. 48 days, P<0.001). Evaluation of the bone marrow at the time of death revealed ~2.5 fold decrease in the frequency of LSCs (P<0.01) and ~2 fold increase in the percentage of cycling LSCs (in SG2M) (P<0.001). Analysis of RNA-seq data from miR-99 KD LSCs revealed induction of a differentiated normal progenitor signature (P<0.001) and depletion of a shared HSC/LSC gene signature (P=0.05). Giemsa staining of peripheral blood showed miR-99 KD also induced a significant increase in the number of differentiated myeloid precursors in the peripheral blood (P<0.001), reminiscent of AML differentiation-inducing agents used in the clinic such as ATRA. Consistent with a role in regulating leukemic blast differentiation, microRNA-Seq data from the 153 AML patients in the TCGA database revealed that miR-99 expression inversely correlated with their French-American-British classifications, with low expression levels associated with M4 and M5 subtypes. Compatible with a role in maintaining LSCs, miR-99 KD in a primary AML sample reduced long-term engraftment upon xenotransplantation into NSG mice, and the engrafting cells displayed increased CD14 expression. Together, these data demonstrate that similar to normal HSPCs, miR-99 maintains leukemic blasts in the undifferentiated state and support LSC function. As miR-99 restricts differentiation in both LSCs and HSCs, we asked which miR-99 target genes mediate miR-99 KD phenotypes. To address this question, we performed a shRNA library-based forward genetic screen designed to rescue the reduced HSC function following miR-99 KD. We designed 180 shRNAs against 45 predicted miR-99 targets that we identified as upregulated upon acute miR-99 KD in mouse HSPCs. Among the conserved miR-99 targets, Hoxa1, a member of the Hox family of transcription factors, was among the top hits, with all 4 shRNAs being enriched compared to controls. Ectopic expression of Hoxa1 in MonoMac6 AML cells was sufficient to induce differentiation, a phenotype similar to miR-99 KD. These data indicate that Hoxa1 is an important downstream mediator of miR-99 function.

Abstract:
In this talk, I review a nonparametric method for the collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. In the second part of the talk, I present an extension of this approach for the simultaneous estimation of spectral density functions (SDFs) for a collection of stationary time series that share some common features. A collective estimation approach pools information and borrows strength across the SDFs to achieve better estimation efficiency. Also, each estimated spectral density has a concise representation using the coefficients of the basis expansion, and these coefficients can be used for visualization, clustering, and classification purposes. The Whittle pseudo-maximum likelihood approach is used to fit the model, and an alternating blockwise Newton-type algorithm is developed for the computation. A web-based shiny App found at “https://ncsde.shinyapps.io/NCSDE” is developed for visualization, training and learning the SDFs collectively using the proposed technique. Finally, we apply our method to cluster similar brain signals recorded by the electroencephalogram for identifying synchronized brain regions according to their spectral densities.

Biography:
Mehdi Maadooliat is a faculty member of the Department of Mathematical and Statistical Sciences at Marquette University. Mehdi is also affiliated with Marshfield Clinic Research Institute as Associate Research Scientist from 2015. He received his BS from the Sharif University of Technology, MS from Marquette and a Ph.D. degree in Statistics from Texas A&M University, where he also served as a post-doctoral fellow. His primary research interests include machine learning, bioinformatics, and functional data analysis. Recently he is working on developments of the statistical models in high-dimensional data structures with application to biological sciences, including, but not limited to genomics and proteomics.

Abstract:
In this presentation, the organ-on-a-chip technology will be introduced and a few chip-based disease models will be discussed. Several future research directions in the field will be highlighted.

Biography:
Alireza Mashaghi is a physicist and a medical scientist at Leiden University and Harvard Medical School. In the course of his academic career, he has been affiliated with various institutions including Max Planck Institute, ETH Zurich, Delft University of Technology, Massachusetts Institute of Technology, and Harvard. At Max Planck Institute, he was involved in the development of fluorescence correlation spectroscopy as well as high-resolution NMR spectroscopy for biological applications. Further, he did postdiploma work in materials science at ETH Zürich, where he designed and conducted various projects on nanotechnology, surface science, and optical/plasmonic sensing. He then moved to the Netherlands where he pioneered the use of single-molecule force methods for studying bimolecular folding processes. He received his Ph.D. with highest distinction in physics from Delft University of Technology. His current research at Leiden and Harvard encompasses a wide range of topics from single-molecule and systems biophysics to clinical medicine. He is an editorial board member of several well-established journals including NanoResearch, Medicine, and Scientific Reports.

Abstract:
Sequencing of tumor nucleic acids that enter the bloodstream provides a non-invasive means for cancer detection and diagnosis. Recent studies demonstrate that tissue-specific gene expression can be inferred from deconvolution of distinctive epigenetically encoded features in cell-free DNA (cfDNA) including DNA methylation, nucleosome positioning, nucleosome phasing at transcriptional start sites (TSS), and proximal enhancer accessibility. Here, we first identified chromatin features in cfDNA that correlate with gene expression, and built predictive models that can estimate expression level from cfDNA. We then developed a targeted method for high-resolution tissue-of-origin classification by epigenetic profile inference from cfDNA sequencing (Epic-Seq). By integrating select chromatin features at the level of individual marker genes, Epic-Seq is able to distinguish cancer plasma samples from normal controls and notably from other histological subtypes of a given cancer type. We further demonstrate that Epic-Seq has broader applications including estimation of cell type fractions in the blood. In summary, we introduce a method for non-invasive determination of gene expression state of genes from cfDNA and propose its wide-ranging applicability.

Biography:
TBA

Abstract:
Microbial prokaryotes, with the estimated abundance of 5×1027; are at the base of food web in groundwater habitats that host all domains of life plus viruses. While microbial diversity has been probed by large-scale omics studies in the shallow aquifers, a CO2 influenced geyser, and carbon rich shales; their viability, dynamics, and interactions in the pristine and extremely oligotrophic deep groundwater remained understudied. Here we present an extensive multi-omics survey of the Fennoscandian Shield deep biosphere using genome resolved metagenomics analysis of 44 sequenced samples with contrasting water age. Samples originate from the Äspö Hard Rock Laboratory, Sweden (depth 170-450mbsl; 731 Gb data) and Olkiluoto, Finland (depth 320-528mbsl; 611Gb data). We have reconstructed ~1300 metagenome assembled genomes (MAGs); augmented our dataset with 114 single cell amplified genomes (SAGs), and explored their active metabolism using metatranscriptomics. The reconstructed genomes span over the prokaryotic tree of life, showing the remarkable diversity of the deep biosphere and the distinct metabolic capabilities of resident communities depending on the water origin and available energy sources. DPANN archaea and candidate phyla radiation (CPR) representatives that typically have extremely streamlined genomes and harbor a reduced metabolism numerically dominate the prokaryotic community. Genome replication analysis shows active replication for these taxa reinstating the importance of syntrophy in extremely oligotrophic habitats. Coexistence of these groups with the larger genome size chemotrophic and heterotrophic prokaryotes implies the importance of adaptability for niche occupation and puts forward the leaky genetic functions and interactions as the major determinant of developing a successful population in the deep biosphere.

Abstract:
TBA

Biography:
Mohammad Reza Ejtehadi obtained his Ph.D. in physics from the Sharif University of Technology, Tehran, in 1998. He has worked at the Max-Planck Institute for Polymer Research in Mainz and the University of British Columbia in Vancouver, and in 2004 he joined the Sharif University of Technology, where he has held a professor position since 2014. He applies statistical physics and simulation to various problems in soft matter and biological systems. He was also elected as the president of the Physics Society of Iran in 2017.

Abstract:
In this talk, I'll provide some most recent findings of my lab about developing algorithm, statistical approaches and deep neural networks for different biomedical problems as well as how we're translating them into clinics

Biography:
He received his B.Sc. and M.Sc. in computer engineering from Sharif University of Technology, and Ph.D. in bioinformatics from University of Tehran. He has been a bioinformatics researcher and head of bioinformatics lab at Royan Institute for Stem Cell Biology and Technology. He was a research associate at the Max Planck Institute of Molecular Biomedicine, and postdoctoral fellow of Bioinformatics in Colorado State University. He is currently Assistant Prof. of Bioinformatics in Computer Eng. Department, Sharif University of Technology. He is also a gold medalist of 12th International Olympiad in Informatics (IOI).

Abstract:
Lung cancer is genomically diverse and remains the leading cause of cancer death worldwide with lung adenocarcinoma being the most common subtype. The development of targeted therapies for lung adenocarcinoma patients with oncogenic EGFR mutations or ALK, RET, or ROS1 translocations has greatly advanced clinical care and extended patient survival. However, about one third of lung adenocarcinomas lack known oncogenic drivers (representing over 200,000 patients per year worldwide) and thus lack these precision therapy options. In order to develop targeted therapy for these patients, it is necessary to identify key genomic alterations that contribute to oncogene-negative tumor initiation and growth. Drivers in oncogene-negative lung tumors could be yet uncharacterized oncogenes, purely epigenetic modifications, or inactivation of single or combinations of tumor suppressors. Tumor suppressor mutations are enriched in oncogene-negative lung adenocarcinomas compared with tumors with known oncogenic drivers. However, the high rate of genomic alterations in lung adenocarcinomas complicates the identification of key driver genes in tumors without known oncogenic drivers. We hypothesized that combinations of tumor suppressor gene inactivation may enable the development of at least a subset of tumors without known oncogenic driver mutations. Here, we integrate Cre/Lox and somatic CRISPR/Cas9-genome editing to perform a broad analysis of the impact of pairwise alterations of tumor suppressor genes on lung tumor development in mouse models. To quantify the effect of inactivating single and pairs of tumor suppressor genes on lung cancer initiation and growth in a high-throughput manner, we generated over 200 different genotypes in parallel in mice. We delivered barcoded lentiviral-Cre vectors expressing single guide RNAs targeting a pool of tumor suppressor genes to the lungs of mice with floxed alleles of Pten, Tp53, Lkb1, Keap1, and Nf1 as well as Cre-regulated fluorescent protein reporter and Cas9 alleles. One year after lentiviral transduction, we observed that inactivation of specific combinations of tumor suppressor genes can act as a tumor-driving event in lung cancer. Currently we are analyzing the nature of the engineered genetic alterations through high-throughput sequencing of barcoded regions, characterizing tumors at molecular and cellular levels, and validating these results. Our study sheds light on biology of oncogene-negative tumors and opens an avenue for the rational design of targeted treatment strategies for patients with these types of tumors.

Biography:
I have been working on stem cell biology and oncology for the past 9 years during my postdoctoral training with Dr. Monte Winslow at Stanford University, Ph.D. with Dr. Christopher Lengner at the University of Pennsylvania, and M.S.c. at the University of Tehran. My extensive experience includes the use of genetically engineered mouse models, Next-Generation Sequencing, pharmacogenomic analysis, and CRISPR/Cas9 genome editing to discover molecular pathways regulating stem cell self-renewal, tissue regeneration, tumor initiation, and drug response. I have been using this knowledge to regulate these pathways pharmacologically and using environmental cues such as nutrient modulation and calorie restriction to achieve desirable outcomes such as protection of epithelial tissues against injuries frequently caused by conventional cancer treatments such as radiotherapy. My long-term career goal is to use my rigorous training in molecular biology, regenerative medicine, and oncology to design efficient and safe drugs for cancer therapy. The research and training available at the Stanford University and UPenn were ideal for me to grow as an independent and collaborative researcher. I gained proficiency in the use of the mathematical modeling and became capable of working productively with computational and mathematical collaborators. The strong connection between medical systems of these Institutes and research laboratories provided me with additional translational training through frequent interactions with clinicians to bridge the clinical-basic science gap. I have contributed to many projects, cultivated a mentoring style that motivate younger researcher, and gained skills of presenting data in a coherent and articulate manner to different audiences.

Abstract:
TBA

Biography:
I received my Master degree in Medical Biotechnology from University of Tehran (Iran) in 2005, investigating the efficiency of biodegradable nanoparticles for DNA vaccine administration in mouse models of allergy. I then started my PhD in Molecular Medicine (Pharmacology) at the Institute of Experimental and Clinical Pharmacology at Medical University of Graz (Austria), where I studied potential drug targets (G Protein-Coupled Receptors, GPCR) involved in inflammation. After graduation in 2010, I started a 3-year postdoctoral work at Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH/NIAID). At this position, I studied the impact of Regulators of G-protein Signaling (RGS) on the pathogenesis of asthma ex vivo and in vivo. This was followed by a 1-year postdoctoral work at University of Maryland School of Medicine exploring the mechanisms by which RGS proteins disturb the body calcium homeostasis. In 2015, I joined the Division of General & Oncologic Surgery at the Department of Surgery, University of Maryland School of Medicine as an assistant professor.

Abstract:
Adipose tissue plays a key role in systemic metabolism. There are two functionally distinct types of adipose tissue: white adipose tissue (WAT) is the major reservoir of energy, while brown adipose tissue (BAT) and its related beige fat are specialized for energy expenditure. Although numerous studies have demonstrated the presence of multiple cell types in adipose tissue, our understanding of heterogenous adipose tissue niche is limited. Additionally, different adipose depots undergo massive remodeling in response to environmental changes, such as cold and diet. Here, we harnessed the power of single cell RNA-sequencing (scRNA-seq) to uncover the cellular composition and temperature-dependent remodeling of BAT, WAT, and beige adipose tissue niche with single cell resolution. We identified distinct subpopulations of BAT and WAT precursor cells, immune cells, endothelial cells, and vascular smooth muscle cells in the SVF of each depot. Our analysis revealed novel markers that specifically mark brown and white adipocyte precursors and provided new insights into the coordinated changes in niche factors that accompany and support the functional adaptation to the ambient temperature. By comparing the transcriptional landscape of each component of the BAT and WAT niches from mice at different temperatures, we mapped distinct cellular states and transitional events leading to functional and structural remodeling of adipose tissue in the process of BAT activation, beiging of WAT, and whitening of BAT. In summary, scRNA-seq of BAT and WAT provides a high-resolution map of different cell types within their niche and suggests the critical contribution of these cell types to depot specific functions, tissue homeostasis, and turn over capacity.

Abstract:
Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading frame in myofibers, cardiomyocytes, and muscle stem cells after local or systemic delivery. AAV-Dmd CRISPR treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.

Biography:
Sharif Tabebordbar is a postdoctoral fellow in the Sabeti lab. Sharif’s research is focused on engineering adeno-associated viruses (AAVs) to develop tissue-specific gene delivery vehicles and to improve safety of AAV-mediated gene delivery for gene editing applications. Sharif received his BSc and MSc degrees in biotechnology from University of Tehran and his Ph.D. in Developmental and Regenerative Biology from Harvard University. During his Ph.D., he developed culture conditions to expand healthy and diseased adult muscle stem cells in culture and provided the proof of concept for correcting the genetic mutation in these cells using gene editing technology. He also provided evidence for the feasibility of an in vivo gene editing-based approach to treat Duchenne Muscular Dystrophy (DMD) and investigated the host immune response after delivery of gene editing components into animals. The results of his research have been published in several peer-reviewed journals including Cell, Science and Nature Methods. Sharif is also the recipient of Distinction in Teaching Award from Derek Bok Center for Teaching and Learning at Harvard, Albert J. Ryan Foundation Award for Outstanding Graduate Students in Biomedical Sciences, Excellence in Research Award from American Society of Gene and Cell Therapy and Royan International Research Award in Regenerative Medicine. Sharif’s research in the Sabeti lab is partly supported by the Merkin Institute for Transformative Technologies in Healthcare.