About the Tesar Lab

Research

A longstanding and central question in biology is how a single cell, the fertilized egg, generates all the diverse cell types of the body. Our laboratory is primarily interested in the molecular mechanisms by which cells acquire specific identities during development and maintain those identities as adults. We use stem cells to understand mammalian development and associated diseases.

We focus on three general questions:

1. How do pluripotent cells (those that can become any cell type in the body) differentiate into specific cell fates?

Approach: We use mouse & human embryonic stem cells and mouse epiblast stem cells to interrogate the intrinsic and extrinsic signals that direct cells into specific fates.
Impact: Understanding of developmental signals provides insight into why perturbations cause disease. Additionally, these studies provide a mechanism to produce functional cell types for potential use as direct cellular therapeutics or drug screening platforms.

Current Projects:
-Epigenetic and transcription regulation of cell state during gastrulation and neural development
-Differentiation of pluripotent stem cells into functional neural fates (specifically glial lineages such as oligodendrocytes)
-High throughput drug screening for modulators of stem cell differentiation

2. How do differentiated cell types maintain their identity?

Approach: We modify transcription factor programs to induce cells to switch fates.
Impact: Understanding the mechanisms underlying cellular identity allows for the prevention of revertant/aberrant cell fates (i.e. cancer). Additionally, these studies may allow for production of clinically useful cell types for therapy.

Current Projects:
-Reprogramming of adult cells into pluripotent stem cells (iPS cells)
-Reprogramming of non-neural cells directly into neural fates

3. What are the genetic and epigenetic mechanisms that contribute to developmental disorders?

Approach: We use induced pluripotent stem cells from human patients with neurodevelopmental disorders to study the cellular and molecular aberrations that contribute to disease.
Impact: Unlike other species, access to developing human tissues is not feasible. iPS cell and direct reprogramming technologies allow access to pluripotent cells from individual patients. By comparing iPS cells from different patients, we have a tractable system to study human developmental genetics and uncover new genetic or pharmacological therapies.

Current Projects:
-Use of iPS cells to compare neural development between control patients and patients with mental health disorders
-Use of iPS cells to compare neural development between control patients and patients with neurodevelopmental disorders
-Screening of new therapeutics to modulate patient-specific phenotypes