Malaiyalam Mariappan, PhD

Assistant Professor of Cell Biology

Research Interests

Alzheimer Disease; Cell Biology; Diabetes Mellitus, Type 2; Endoplasmic Reticulum; Quality Control; Prion Diseases; Neurodegenerative Diseases; Unfolded Protein Response

Research Organizations

Cell Biology: Membrane Traffic

Faculty Research

Research Summary

Protein Quality Control and Human Diseases: Our laboratory is interested in understanding how cells detect misfolded proteins and prevent protein aggregation in the cell. Since cells are continually exposed to various stress stimuli, proteins have a high probability of mislocalization, misfolding, aggregating, and causing cellular toxicity and human diseases. To tackle these problems, eukaryotic cells have evolved sophisticated molecular machinery for detecting and eliminating of misfolded proteins in the cell. Our goal is to identify and understand the components involved in various cellular quality control processes.

Currently, our lab is focusing on how the endoplasmic reticulum associated degradation (ERAD) pathway accurately recognizes misfolded proteins in the ER and retro-translocate them into the cytosol. How these retrotranslocated proteins are delivered to the proteasome for degradation (Figure 1A). Our second goal is to understand how the UPR sensors (IRE1, ATF6, and PERK) detect misfolded proteins in the ER and transduce the information to the cytosol and nucleus to upregulate chaperones for improving the ER folding capacity (Figure 1B). Our third goal is to figure out why dysfunction or overloading of proteasomes leads to accumulation and aggregation of misfolded proteins in the cytosol. How these protein aggregates affect the cellular physiology to cause many devastating neurodegenerative diseases including Alzheimer's, Retinitis Pigmentosa and prion diseases (Figure 1C). We use a variety of techniques, including molecular genetic analysis in tissue culture cells, biochemical, structural and high-resolution imaging approaches.

Selected Publications

Full List of PubMed Publications

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Contact Info

Malaiyalam Mariappan, PhD
Lab Location
West Campus, Ste B-24/2nd Floor/Rm-219
West Haven, CT 06516
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Mariappan Lab