Reginald Halaby

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PROFILE:
Dr. Reginald Halaby is a Professor of Biology at Montclair State University and a cancer scientist with nearly 30 years of specialized research in lysosomal-mediated cell death.

His laboratory has focused on one of oncology’s most urgent challenges: killing cancer cells that have evolved resistance to conventional therapy. Standard chemotherapy induces cell death through apoptosis, a pathway that tumor cells frequently escape by silencing key proteins such as caspase-3. Dr. Halaby’s research demonstrates that lysosomal-mediated apoptosis (LMA) offers a mechanistically independent alternative: by disrupting the lysosomal membrane and releasing cathepsin proteases into the cytosol, LMA triggers cell death in tumors refractory to conventional treatment.

His laboratory’s central finding: triptolide, a natural lysosomotropic compound derived from the Chinese herb Tripterygium wilfordii (Thunder God Vine), induces lysosomal membrane permeabilization and kills caspase-3 deficient, apoptosis-resistant breast and prostate cancer cells at concentrations 1,000 times lower than conventional chemotherapy, validated in athymic mouse xenograft tumor regression models.

Dr. Halaby has presented this work at multiple American Association for Cancer Research (AACR) Annual Meetings, secured NIH funding including a $1.8 million NIH MARC grant, and received the AACR Minority Scholar in Cancer Research Award. He serves on the Editorial Board of the Journal of Molecular Biology and Molecular Imaging and is a reviewer for several oncology publications.

Dr. Halaby earned his Ph.D. and M.Phil. in Biology from The City University of New York, completed postdoctoral training in cancer research at the Adirondack Biomedical Research Institute, and holds a B.A. in Biology from Boston University.

SPECIALIZATION:
Lysosomal-mediated apoptosis (LMA) in chemoresistant human breast and prostate cancer cells. Dr. Halaby’s laboratory has demonstrated that triptolide, a natural lysosomotropic agent derived from Thunder God Vine, induces lysosomal membrane permeabilization and cell death via a caspase-3 independent mechanism. These findings are significant because malignant cells have larger and more active lysosomes compared to control cells, making them vulnerable to lysosomotropic agents, like triptolide. Conventional anticancer therapies are non-specific, killing neoplastic and healthy cells. Dr. Halaby’s team is developing novel targeted anticancer strategies.

Active research areas include lysosomal membrane permeabilization (LMP), cathepsin-mediated cell death, autophagy-lysosome pathway modulation, natural product-based anticancer mechanisms, and in vivo xenograft tumor regression models.

Specialization

Induction of lysosomal-mediated apoptosis in chemoresistant human breast and prostate cancer cells using triptolide (Thunder God Vine), a Chinese herb that has been used in traditional Chinese medicine for over two centuries. We have shown that triptolide's apoptotic abilities are due, in part, to it being a lysosomotropic agent.

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Research Projects

Targeting lysosomes in cancer as a therapeutic approach against apoptosis-resistant tumors

Cancer cells become resistant to treatment protocols by mutating their DNA sequence: inactivating pro-apoptotic and tumor suppressor genes; activating oncogenes; etc. Furthermore, most chemotherapy drugs are nonspecific, killing all rapidly dividing cells including healthy ones. Cancer cells possess larger and more active lysosomes compared to normal cells. Therefore, targeting lysosomes may lead to the design of novel, more effective anticancer drugs.

Lysosomal-mediated programmed cell death as an anticancer treatment modality.

Lysosomes contain approximately 50 degradative enzymes that have the capability of digesting all of the molecules of a cell. Our results demonstrate that triptolide modulates lysosomal membrane permeability in such a way that it results in the release of the lysosomal enzymes, such as cathepsin B, into the cytosol. Furthermore, we show that triptolide induces lysosomal-mediated cell death in MCF-7 breast and DU-145 prostate cancer cells. This work is significant because MCF-7 cells lack caspase-3, a key executioner protein in the intrinsic and extrinsic apoptotic pathways. We and others have shown that tumors that contain mutant or deficient caspase-3 become treatment-resistant. Therefore, lysosomal-mediated cell death provides an important alternative mechanism for eliminating apoptosis-resistant tumors.

MCF-7 cells lack the caspase-3 protein due to a mutation. This protein plays a key role as one of the executioner caspases in the apoptotic pathways. Furthermore, it has been shown by others that cancer cells that are deficient for caspase-3 acquire resistance to chemotherapy and/or radiation. Therefore, our hypothesis is that lysosomal-mediated programmed cell death, which we have demonstrated is independent of caspase-3, may be utilized to treat apoptosis-resistant cancer cells.

We have demonstrated that triptolide exerts its anticancer effects via a lysosomal-mediated mechanism. The significance of these findings is that triptolide may serve as a novel natural anticancer agent that is effective against apoptosis-resistant (chemotherapy-resistant and radiation-resistant)tumors.

Triptolide induces apoptosis via a lysosomal mechanism

We provide evidence suggesting that triptolide disrupts the lysosomal membrane, which results in the leakage of lysosomal enzymes to the cytosol where the enzymes trigger the intrinsic apoptotic pathway.

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