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Personal Statement

I have extensive experience performing pluripotent and neural stem cell research, as well as generating human induced pluripotent stem cells (iPSC) for re-creating human "disease-in-a-dish" models. I have published high-profile papers on human iPSC-based disease modeling in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Since 2011, I have developed and directed the Cedars-Sinai iPSC Core, where my group has optimized generations of non-integrating iPSC lines routinely and with great efficiency in defined media and substrates. My team has now generated >85 iPSC lines from patients with keratoconus, SMA, ALS, Huntington's disease (HD), skeletal dysplasia, inflammatory bowel disease, MCT8-specific thyroid hormone cell-membrane transporter deficiency and neurofibromatosis Type 1 using fibroblasts, mesenchymal stem cells, adipose, epithelial, corneal keratocytes, lymphoblastoid cells and fresh whole blood for reprogramming to iPSC. The Sareen Lab is also the chief site for the National Institutes of Health- and California Institute for Regenerative Medicine-funded HD iPSC repository. The Sareen Lab routinely differentiates patients' iPSCs to neural stem cells and regionally specified cells of the central and peripheral nervous system, including spinal motor, gamma-aminobutyric acid, dopamine and striatal neurons, Schwann cells, astrocytes, and oligodendrocytes. We have also generated techniques to make multipotent neural stem cells and motor neuron precursor directly from iPSC, allowing differentiation into many neural cell types. I have previously characterized pharmacological pathways and Ca2+-signaling mechanisms of resveratrol-induced human tumor cell death, while simultaneously participating in its preclinical drug-development process.

My Laboratory is interested in the molecular pathogenesis underlying neurodevelopmental and degenerative diseases to develop novel tools for drug screening and dissecting mechanisms for motor neuron degeneration in SMA and C9ORF72 repeat-expansion associated ALS. Using the iPSC platform, we are studying the molecular basis of signals that converge in the brain to impact metabolism and energy homeostasis during Type 2 diabetes and obesity. By using stem cells to investigate the neurobiology of metabolic and hormonal regulation connections between brain centers (i.e., hypothalamic, pituitary, endocrine and autonomic pathways, which regulate energy homeostasis, metabolic rate, and hormonal equilibrium), we hope to find better treatments for some of these intractable diseases. Specifically, we want to understand how hormonal regulation from the stomach, fat, and pancreas cause neuroinflammation, rewiring and impairment of neural cells in areas of the brain that regulate feeding behavior in obese and lean individuals. At the confluence of all these programs, we are actively utilizing principles of organogenesis and bioengineering to create iPSC-based complex multidimensional models, i.e., organs-on-a-chip. Collectively, the Sareen Laboratory has significant expertise in iPSC reprogramming technology and generating various central nervous system cell types from pluripotent stem cells for disease modeling and screening assays to test direct molecular therapeutics by high-content methods.

Contact the Sareen Lab

8687 Melrose Ave., Suite B227
West Hollywood, CA 90069