Research in the Lab

Graduate students and postdoctoral scholars in the lab investigate three interconnected areas of research: immune cell signaling, immune dysfunction, and protein regulation. Our work focuses on understanding how immune signaling pathways operate under normal conditions and how disruptions in these pathways contribute to inflammatory disease, autoimmunity, and cancer.

Immune Cell Signaling

A major focus of the lab is the earliest signaling events that occur at the cell membrane, beginning with receptor ligation and activation of membrane-proximal protein tyrosine kinases such as Src, Lyn, Fyn, Hck, Fgr, and Syk.

We study how receptor engagement shapes downstream signaling output and how networks of kinases and phosphatases are selectively mobilized in response to different stimuli. Our work also examines the negative feedback mechanisms that restrain inflammatory responses, helping maintain immune balance.

Immune Dysfunction

Our research also investigates how myeloid cells distinguish between different inflammatory ligands to generate appropriate immune responses. We examine how baseline cellular states influence responses to pro-inflammatory signals and how immune cells can become dysfunctional.

In some cases, immune cells bypass normal regulatory checkpoints, resulting in hyperinflammatory or immunosuppressive states. By identifying the molecular mechanisms that drive these dysfunctional responses, we aim to uncover key regulatory proteins that could be targeted therapeutically in autoimmune disease and cancer.

Protein Regulation, Structure, and Dynamics

The lab also studies the fundamental mechanisms that regulate signaling proteins, including protein–protein interactions, localization, and energetic constraints that control activation and inhibition.

Using structural biology, biophysics, and structure-guided mutagenesis, we investigate questions related to protein dynamics, allosteric regulation, and dimer formation in membrane-proximal signaling proteins. Our recent work focuses on dimerization of the tyrosine kinase Csk, the master negative regulator of Src-family kinases.

View Freedman publications  

Looking for current Freedman Lab Info or for all of CFI Graduate Students, Post Doctoral Fellows or Research Associates?