Our Science – Kwong Website
King F. Kwong, M.D.
The Kwong lab is focused on identifying key alterations in cell death mechanisms, in which apoptosis is one example, that contribute to tumor survival, from the earliest stages of tumorigenesis to advanced disease such as metastasis, and the development of novel targeted agents directed towards re-activating cell death pathways to render cancer cell arrest, and ultimately cancer cell death.
Programmed cell death, or apoptosis, is one example of a highly phylogenetically conserved intracellular process and is one of the key core pathways of cancer. The proteins and regulatory elements of apoptosis are found in many cell types; but in the cancer cell, apoptosis regulation is commonly altered by genetic changes or selection to render less effective its intrinsic ability to keep host cells in check and to destroy cells potentially detrimental to the host organism. Fundamentally, apoptosis, when well-functioning, is an efficient method to eliminate cells that disrupt the homeostasis of the organism. Apoptotic cell death is characterized morphologically by an orderly sequence of proteolytic destruction of DNA degradation, nuclear fragmentation, and cytoplasmic involution. Homologues of the members of the apoptosis pathway, such as those in the caspase family and the inhibitors of apoptosis (IAPs), have been identified in organisms ranging from C. elegans to H. sapiens (humans), thus reinforcing the importance of an intact, properly functioning, apoptosis system.
Our current work in the laboratory is directed at better understanding how altered cell death pathways and oncogenic drivers contribute to cancer cell survival and to determine strategies to overcome these molecular barriers in order to translate our laboratory work into novel therapeutic regimens for patients. Specifically, we have an active interest in identifying and deciphering how small non-coding RNAs regulate the apoptosis and cell death/survival pathways. As an example, we have discovered that a specific microRNA (hsa-miR-24) is responsible for regulating the expression of XIAP in cancer cells, a key member of the IAP family and barrier to cell death. Additional investigations are being conducted to elucidate the mechanisms leading to the development of lung cancer metastasis and to identify new methods for treating metastatic disease. In this area, we have studied how to improve the delivery of siRNAs as nanotherapeutics and it has led to our recent discovery and engineering of a multi-component biocompatible nanoparticle which engages the cancer cell's internalization pathways to result in markedly increased bona fide uptake of siRNA-loaded nanoparticles selectively into cancer cells, release of siRNA inside the cancer cells, and robust on-target effects in vivo. The current direction of our translational efforts is centered on re-activation of impaired cell death mechanisms and attenuation of tumor cell survival stimuli in cancer cells via novel small molecule drugs and biocompatible synthetic nanomolecular contructs.
This page was last updated on 11/8/2013.