Black Family Stem Cell Institute

Stem Cell Metabolism and Aging

Metabolic properties of stem cells are intertwined with stem cell behavior in the laboratory and in the physiological environment of the animal in vivo.

Stem cell function is often compromised by their maintenance in a dish in vitro. Elucidating the mechanisms that influence stem cell metabolism will be invaluable for the maintenance and expansion of stem cells in the laboratory for therapeutic purposes. At the Black Family Stem Cell Institute investigators have dedicated significant efforts to unravel the metabolic properties of stem cells.

Aging is associated with a decline in tissue regeneration leading to increased degenerative disease and cancer. Researchers believe that this age-related decline in tissue function is at the root of overall organismal aging. Stem cells maintain tissue homeostasis by regenerating damaged or lost cells and tissues during their lifetime. Stem cell function declines with age in many tissues, including blood, skin, brain, and skeletal muscle. Age-related modulations of stem cell properties, including their interactions with a changing environment, are thought to contribute to their regenerative decline with age. The decline of the regenerative capacity of stem cells with age compromises tissue integrity and may promote organ failure and diseases of aging. Identifying regulators of stem cell aging is of major significance for public health because such regulators may contribute to promoting healthy aging and be valuable therapeutic targets to fight disorders of aging, such as cancer and Parkinson’s disease. Investigators at the Institute are greatly motivated to elucidate mechanisms of stem cell aging in various tissues. In these efforts, we focus on the modulation of stem cell metabolism with age and its influence on stem cell epigenetics.

Investigators with a major focus in the stem cell metabolism and aging include:

Timothy A. Blenkinsop, PhD

Timothy A. Blenkinsop, PhD, is an Assistant Professor in the Department of Cell, Development, and Regenerative Biology at the Icahn School of Medicine at Mount Sinai, as well as member of the Ophthalmology Department, the Black Family Stem Cell Institute, and Mount Sinai’s Eye and Vision Research Institute. His team is interested in understanding human retina development in normal and pathological situations, as well as in modeling in vitro various eye diseases. The lab’s primary interest lies in retina stem cell biology, cell replacement therapy, and endogenous retina regeneration potential. The lab uses adult human tissues and pluripotent stem cells-derived differentiated cells to probe retina physiology and model diseases such as age-related macular degeneration, proliferative vitreoretinopathy, and proliferative diabetic retinopathy. The main goal is to identify epigenetic regulation of cell plasticity for stimulating it with therapeutic benefit, while also modeling diseases where plasticity leads to disease.

Ongoing research interests include:

  • Exploring signaling transduction pathways involved in retinal pigment epithelium plasticity
  • Exploring cell replacement therapy for age-related macular degeneration
  • Researching cell fate specification of developing human eye field

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Joseph Castellano

Joseph Castellano, PhD is an Assistant Professor of Neuroscience and Neurology and member of the Friedman Brain Institute and the Ronald M. Loeb Center for Alzheimer’s disease at the Icahn School of Medicine at Mount Sinai. Understanding the mechanism by which aging acts as a major risk factor for neurodegenerative disorders is critical as the aging population increases in the coming decades. Recent work has demonstrated that age-related changes in neural cells of the neurogenic niche within hippocampus are regulated by cues present in the systemic environment. Research in the Castellano laboratory is focused on understanding the molecular mechanisms underlying such blood-CNS communication, as well as the extent to which this communication shapes development of brain neuropathology in neurodegenerative diseases. Towards the goal of developing novel therapies that exploit this putative communication, the laboratory is interested in identifying and defining youth-associated activities that can rescue aspects of Alzheimer’s-related pathology. The Castellano laboratory specializes in a wide range of genetic tools in mouse models to answer complex physiological and compartmental questions related to brain function. Multiple levels of analysis are incorporated in the laboratory’s experimental aims, including editing in cell culture, human disease modeling in mice via viral-mediated and cell transfer tools, and cognitive behavioral assays. A focused goal of the group is to characterize the mechanism by which novel blood-borne factors mediate changes in function in the hippocampus.

Ongoing research interests include:

  • Characterizing mechanism of action of blood-borne factors within hippocampus
  • Understanding the role of genetic risk factors in regulating blood-brain communication in the context of disease.
  • creation of novel humanized mouse models to understand neuroimmune function in the context of disease pathology.

Saghi Ghaffari, MD, PhD, is a Professor of Cell, Developmental, and Regenerative Biology and a member of The Tisch Cancer Institute. Her lab studies mechanisms that sustain blood forming stem and progenitor cells (HSPCs) throughout life and that are perturbed in disease. Her team is particularly interested in programs that maintain quiescence of blood-forming stem cells, a property that determines the potency and overall regenerative capacity of adult stem cells and that is lost with age. Quiescence is also a mechanism by which malignant stem cells resist therapy. To attain this goal, the Ghaffari Laboratory has been investigating metabolic and mitochondrial-related programs and organelle communications in young and aged HSPCs. The Ghaffari lab uses a variety of approaches, including various omics, super resolution imaging, and gene modulation technology combined with genetically modified mouse models and human cells to address these questions.

Ongoing research interests include:

  • Investigating mechanisms that control mitochondria-lysosome communication in normal mouse and human hematopoietic stem cells (HSCs) in aged HSCs and in leukemic stem cells
  • Exploring transcriptional and epigenetic programs that regulate organelle biogenesis in HSPCs and their alteration with age
  • Investigating metabolic and redox regulation of erythroid cell maturation and identifying mechanisms and components of mitochondria-nucleus communication during this process
  • Elucidating mechanisms of apoptosis in beta-thalassemia

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