Recent Research Projects

Chemical and Genetic Interrogation of Human HSC Self-Renewal: Towards Optimal Cord Blood Grafts

2015/16-2018/19 • $2,667,324 • PI,Other
HSC/progenitor cell (HSPC) transplantation can cure many hematological diseases when patients have a HLA-matched donor. For mismatched patients, the use of cord blood (CB) is ideal thanks to its immature immune system. As most CB grafts suffer from low cell numbers insufficient for adults,...

Development of small molecule modulators of Ras signaling

2017/18-2018/19 • $344,250 • PI,CO
Activating mutations in Ras genes are among the leading drivers in human cancer. The prevalence of Ras genetic lesions is especially high in pancreatic (>90%), colorectal (50%), and lung (30%) cancers. We propose herein a two-pronged strategy to develop small molecule modulators that will block...

Examining chemical modulation of kinesin-13 activities: From mechanism to validation

2017/18-2018/19 • $338,130 • PI,CO
Microtubules (MTs) are protein polymers that form a cable-like network of transport super-highway to move important cargoes around inside a cell. One of these cargoes is our chromosomes, the genetic material that makes us what we are. It turns out that these cables need to grow and shrink all...

RAS-MAPK signal transduction in normal and cancer cells

2018/19 • $330,200 • PI,Other
RAS proteins are key regulators of cell division. Significantly, over a third of human cancers are associated with activating mutations in RAS genes, which makes them the most frequently mutated oncogenes. Yet, despite considerable efforts, there are still no approved drugs that suppress...

Automated Parallel Synthesis of Cyclic Peptide Libraries for Drug Discovery in the Ubiquitin-Proteasome System

2012/13-2014/15 • $120,000 • Scholarship/Fellowship,Other
Proteins are the workhorses and building blocks of life. A tremendous range of tasks at this microscopic cellular level must proceed in concert to maintain health. This is facilitated by a complex communication and control system that depends on a constant flux of associations and dissociations...

Targeting the degradation of the cyclin-dependent kinase inhibitor p21 as a novel approach to cancer therapy

2011/12 • $160,000 • PI,CO
The proliferation of cells is regulated by a complex network of biochemical reactions that ensure that each cell division step is performed correctly and in proper sequence. Among these reactions is the timed degradation of cellular regulatory proteins by an enzymatic system known as the...

Patents

IMIDAZOPYRIDINE, IMIDAZOPYRIMIDINE AND IMIDAZOPYRAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS

Disclosed is a compound of Formula I or a salt thereof, in which X, X1, X2, R1, R2, and R3 are described herein. Also disclosed are pharmaceutical compositions and methods of using the compounds of Formula I to treat disorders mediated by melanocortin-4 receptors.
Related applications: CA20112803448, WO2011CA00783

PYRAZOLOPYRIDINE AND PYRAZOLOPYRIMIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS

Disclosed herein is a compound of Formula I: wherein X, R1, R2, and R3 are as defend herein, or a pharmaceutically acceptable salt thereof to allow the drug to penetrate the cell membrane; or a prodrug, or the compound is labeled with a detectable label or an affinity tag thereof. Also disclosed is a pharmaceutical composition, a method of treating a disorder mediated by melanocortin-4 receptors, and a method of treating obesity using the compounds described.
Related applications: CA20122825098, WO2012CA00089

ASSAY FOR INHIBITORS OF CIP/KIP PROTEIN DEGRADATION

An assay and system compatible with high throughput screening (HTS) that is capable of identifying inhibitors, such as small-molecule inhibitors, of the degradation of the Cdk inhibitor p21, are described. The assay is based on the use of fusion protein comprising (i) a p2 polypeptide; and (i) a reporter protein linked to the C-terminal of said p21 polypeptide, wherein the fusion protein has a half-life that is similar to that of the p21 polypeptide. Inhibitors identified by this assay may...
Related applications: WO2012CA50682, CA20122850410

IMIDAZOTHIADIAZOLE AND IMIDAZOPYRIDAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION

The present invention provides imidazothiadiazole compounds of Formula (I); Wherein W,Y, R0, R2, R4, Ra, Rb, X1, X2, X3 and X4 are as defined herein,, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
Related applications: CA20132871599, WO2013US37884, EP20130719360, EP20130719360, ES20130719360T

HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF

Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of...
Related applications: WO2018CA00206

COMPOUNDS AND USE THEREOF IN THE EXPANSION OF STEM CELLS AND/OR PROGENITOR CELLS

The invention relates to compounds of formula I and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, and autoimmune disease and/or an inherited immunodeficient disease (I).
Related applications: WO2018IB58593