Postdoctoral Scholars of the Siebel Stem Cell Institute

Siebel Postdocs

Mark DeWitt, Ph.D.

I am working to develop novel methods for editing human hematopoietic stem cells (HSCs), the progenitors of all blood cells. HSCs are a prime target for treatment of genetic blood disease by gene editing because changes to these cells will be permanently reflected in all mature blood cells that descend from them. Specifically, I am developing methods for correcting the mutation that causes sickle cell disease, which affects nearly 100,000 individuals in the USA, and millions more worldwide. These methods may eventually form the basis of a cure for sickle cell disease by autologous bone marrow transplant.

Anders Sejr Hansen, Ph.D.
During differentiation, olfactory progenitor cells face a unique cell fate choice: they must choose one, and only one, olfactory receptor (OR) gene out of ~1400 for expression as they differentiate into a mature Olfactory Sensory Neurons (OSN). Incredibly, each OSN expresses only one allele of the chosen OR gene. So somehow, the cell has implemented a random gene regulatory coin flip with a 2800-sided coin. We are attempting to elucidate the causal mechanism underlying singular OR choice by developing an in vitro cradle-to-grave differentiation system that will allow us to directly differentiate primary progenitor cells (HBCs) OSNs and thus observe OR choice as it happens using single-molecule imaging. This allows us to follow the dynamics of key transcription factors and enhancer elements and associate these with OR choice.

Eugene Oh, Ph.D.
Ubiquitylation plays critical regulatory roles in nearly every biological process. Yet little is known of the mechanisms by which stem cells use ubiquitylation to regulate their identity as well as their ability to differentiate into various cell types. With this in mind, I am working to better understand how ubiquitylation shapes stem cell biology.

Audrey Sambeat, Ph.D.
Epigenetic events play a crucial role in stem cell biology during the differentiation process and during cell-fate conversion, and cell fate may be reset by modifying epigenetic marks such as histone modifications or DNA methylation. Elucidating the epigenetic mechanisms involved in the induction of the thermogenic gene program in adult stem cells could make it possible to induce progenitors located in white adipose tissue (WAT) to differentiate into cells whose function is protective against obesity and metabolic disorders. I am working at deciphering epigenetic reprogramming for efficient browning of human adult precursors cells from WAT and the link between epigenetics, environment and metabolism for treatment and prevention of obesity and associated metabolic disorders including type 2 diabetes.

Robert Schinzel, Ph.D.
Complex organisms evolved several stress response pathways in order to navigate an unpredictable and complex environment. Intriguingly, the activation of some of these pathways is not just restricted to cells directly affected by the stress, but can be communicated to distal tissues of the organism.  I am working to identify the mechanisms by which cells communicate and respond to cellular stress by exposing human pluripotent stem cell-derived tissues to toxins or other environmental challenges and asking if the cells are able to communicate their state. Using stem cells allows me to derive a wide range of cell types to understand the tissue-specificity of the communication, as well as the basic mechanism of the signaling, both in healthy cells, and in the context of disease.