Alexey Ladokhin, Ph.D.

Professional Background

1994-2004: University of California, Irvine, CA, Research Scientist
2004-2008: University of Kansas Medical Center, Kansas City, KS, Department of Biochemistry and Molecular Biology, Assistant Professor
2008-2018: University of Kansas Medical Center, Kansas City, KS, Department of Biochemistry and Molecular Biology, Associate Professor
2013-2014: University of California, Irvine, CA. Visiting Associate Professor.
2018 - present: University of Kansas Medical Center, Kansas City, KS, Department of Biochemistry and Molecular Biology, Professor

• BS, Physics, Shevchenko National University, Kyiv, Ukraine
• PhD, Biophysics, Institute of Biochemistry, Kyiv, Ukraine
• Post Doctoral Fellowship, Biochemistry, University of Virginia, Charlottesville, VA
• Post Doctoral Fellowship, Johns Hopkins University, Baltimore, MD

Research

Overview

Major Research Interest

I. Apoptotic regulation by the Bcl-2 protein family
Apoptosis is crucial for proper development and function of cell populations in tissues, and its dysregulation impacts many diseases. Hyperactive apoptosis contributes to neurodegeneration and immunodeficiency, while insufficient apoptosis leads to autoimmunity and cancer, and the ability of cancer cells to avoid apoptosis significantly complicates treatment. The critical step in triggering apoptosis is the permeabilization of the mitochondrial outer membrane (MOMP), which releases apoptotic factors into the cytosol that lead to cell death. MOMP is controlled and executed by the numerous proteins of Bcl-2 family, which include three types: pro-apoptotic pore formers (e.g., Bax), anti-apoptotic pore inhibitors (e.g., Bcl-xL), and BH3-only regulators (e.g., Bid). These proteins directly interact within the mitochondrial outer membrane (MOM) either to promote or prevent protein conformational changes that lead to formation of an oligomeric pore. Our goal is to understand molecular mechanisms of membrane-induced conformational switching in Bcl-2 proteins in regulation of apoptosis.

II. pHLIP and conformational switching on membrane interfaces
The pH-low insertion peptide (pHLIP) is an important tool for drug delivery and visualization of tumors. A traditional explanation for tumor-targeting by pHLIP is its pH-triggered transmembrane insertion. Recently our lab discovered that the presence of 2 mM Ca²⁺, which mimics extracellular conditions, induces pHLIP insertion without the need for acidic conditions. We have reported how changes in lipid composition and presence of divalent cations affect its interactions with model and cellular membranes. We propose that tumor targeting by pHLIP is modulated by the changes in lipid composition of cancer cells (e.g., by exposure of phosphatidylserine to the outer leaflet)

III. Retargeting bacterial toxins to tumors

IV. Biophysical methods