Neal Bennett, PhD
Mentor: Ken Nakamura, MD, PhD
Metabolic Vulnerability in Human Neurons with Impaired Endocytic Recycling
We found that two Alzheimer's disease associated genes (SORL1, ADAM10), conferred a metabolic vulnerability in human neurons derived from iPSCs when knocked down in a survival screen. This result suggests that the metabolic vulnerabilities we observed may be related to a shift in glucose metabolism, and not a change in energy metabolism.
Xinyue Chen, PhD
Mentor: Leor Weinberger, PhD
Targeting PEG10 Positive-Feedback Circuit for Efficient Placenta Generation
My project identifies novel gene circuits that mediate cell-fate conversions. I identified a potential Peg10 positive-feedback circuit. Using new overexpression and reporter strategies, I’m characterizing this Peg10 circuit and its role in trophectoderm specification.
Youjin Lee, PhD
Mentor: Alex Marson, MD, PhD
Utilizing in vivo CRISPR screens to discover key regulators for Treg migration into the central nervous system during autoimmune inflammation
We have recently performed in vivo CRISPR knockout, and CRISPRa (activation) perturbation screens in the animal model of multiple sclerosis and discovered a few novel genes that can positively regulate Tregs to infiltrate the CNS during autoimmune inflammation.
Ankur Garg, PhD
Mentor: Isha Jain, PhD
Understanding the Reversal of Neurological Lesions during Hypoxia Therapy for Mitochondrial Disorders
The goal of this project is to determine the hypoxia rescue mechanism in neurodegenerative disease conditions, more specifically in Leigh syndrome (Ndufs4 KO) and Parkinson’s disease (Htra2 mutant) mouse models. I will use human iPSCs to study the mechanism by which hypoxia has therapeutic benefit in these disease states.
Zoe Grant, PhD
Mentor: Benoit Bruneau, PhD
Capturing the mechanisms of TBX5 haploinsufficiency in development and disease
My research aims to understand the molecular mechanisms regulating dosage sensitivity of the transcription factor TBX5 in heart development. I have generated tagged-TBX5 knock-in cell lines for wildtype, TBX5 heterozygous or deleted iPSCs to study TBX5 proteomics as well as binding across the cardiac genome using ChIP-seq.
Galih Haribowo, PhD
Mentor: Isha Jain, PhD
Understanding The Roles of SLC25A34 in The Hypoxic Adaptation of iPSC-Derived Cardiomyocytes
We recently found that the orphan solute carrier, SLC25A34 is the long-sought mammalian mitochondrial oxaloacetate carrier. We found that SLC25A34 transported oxaloacetate at a higher activity (1.4 fold) than that of yeast oxaloacetate carrier (Oac1p). This result demonstrates that SLC25A34 is indeed an oxaloacetate carrier.
Haruko Kunitomi, MD, PhD
Mentor: Shinya Yamanaka, MD, PhD
Elucidating the roles of translation initiation factors in naïve-state human pluripotent stem cells
We established naïve-state human pluripotent stem cells from CRISPRi-based eIF4G1/2/3 conditional knockdown (cKD) cell lines. Our results suggest that eIF4G2-cKD may alter trophectoderm differentiation. However, the KD efficiency in naïve-state was significantly lower than in primed-state, and now we are generating conditional knockout cell lines.
Zachary Nevin, PhD
Mentor: Bruce Conklin, MD
Allele-specific inactivation of dominant negative FUS mutations
We quantified editing efficiency and specificity of each of our 6 CRISPR/gRNA at the DNA, mRNA, and protein levels using dual-tagged iPSC lines where endogenous FUS genes are tagged with GFP or HaloTag at the N-terminus. Studies in iPSCs and iPSC-derived neurons are in progress.
Tomohiro Nishino, MD, PhD
Mentor: Deepak Srivastava, MD
Determining the Epigenomic and Transcriptomic Consequences by High Glucose in iPSC-Derived Cardiomyocytes Differentiation
We recently found that an Alx3-positive cardiac progenitor subpopulation is selectively sensitive to the event triggered by maternal diabetes using the mouse model of maternal diabetes. We will use the hiPSC-CM differentiation system to dissect the detailed mechanism by which high glucose affects CM differentiation.
Helen Sun, PhD
Mentor: Bruce Conklin, MD
Probing the Mechanism of FUS-ALS/FTD pathogenesis
I engineered an isogenic series of iPSCs that each harbor pathological mutations in FUS, while the FUS alleles are endogenously tagged with either HaloTag or GFP. The mutant FUS and its tag mislocalize to cytoplasmic stress granules, while wildtype FUS remains in the normal location (nuclear), suggesting pathology is due mutant protein acting independently of the wildtype protein.
Yuliya Voskobiynyk, PhD
Mentor: Jeanne Paz, PhD
Cell- and region-specific gene therapy in a mouse model of SLC6A1-related intractable epilepsy
My central hypothesis is that gene therapy targeting thalamic astrocytes or GABAergic neurons will prevent seizures, sleep disturbances, and motor deficits in a new mouse model of SLC6A1-related disorders (SRD). My results demonstrate feasibility to test whether this gene therapy is capable to prevent electrobehavioral deficits in SRD.