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Tufts University

Department of Chemistry

62 Talbot Avenue
Medford, MA 02155
(617) 627-3441

The Kritzer Laboratory

 

The goals of the Kritzer lab are:

1) To discover novel bioactive molecules and to use them to understand human biology and human disease.

2) To maintain a laboratory environment in which knowledge, creativity and hard work lead to success.

3) To provide a tolerant, collaborative, and fun space for us to train as scientists and pursue scientific questions together.

The last half-century has seen a revolution in how we understand and treat disease. The most common plan of attack is to understand disease at the molecular level, then judiciously target key proteins using small-molecule drugs. However, most drugs target only a few types of cellular proteins such as kinases and signaling receptors. Expanding beyond these existing targets could lead to more effective treatments for many diseases, including viral infections, acute and chronic bacterial infections, rare genetic disorders, and currently intractable cancers.

Our lab uses innovative molecules to block disease-associated proteins, often in ways traditional "drug-like" molecules cannot. In one project, we are exploring new ways to synthesize and screen constrained peptides in ever-larger numbers, from several dozen to hundreds of thousands at a time. In another project, we are applying these molecules to control the cellular process of autophagy, which is critical for basic biological processes as well as diseases ranging from lysosomal storage disorders to advanced malignancies.

Discovering new bioactive molecules is only the first step. In several other projects, we are exploring new chemistries that increase the potency and usefulness of bioactive peptides. We are also inventing new methods for measuring cell penetration, which is the most difficult roadblock for many emerging therapeutics including peptide therapeutics, protein therapeutics, RNA therapeutics, and gene editing.

Our research breaks new ground in basic science, and unlocks new avenues for drug development. The hallmarks of our research strategies are efficiency, accessibility, and interdisciplinarity. We have active, federally-funded projects that span organic synthesis, biochemistry, biophysics, computational design, genetics, and cell biology. We are currently working on:

Novel building blocks for controlling peptide conformation

Novel constrained peptide scaffolds with unusual properties and improved cell penetration

Computational design and structural characterization that contribute to design rules for constrained peptides

Translation of newly-discovered molecules from test tube to cell culture to whole-organism models of disease

Novel inhibitors of previously "undruggable" proteins

Novel methods for quantitation of cytosolic penetration for peptide, RNA and protein therapeutics