• Protein engineering
• Cancer therapeutics
• Stem cell reagents
I am presently a Research Scientist (since January 2011) and part of the research team at Minerva Biotechnologies in Waltham, Massachusetts. I am leading projects in two research areas. One is focused on the development of anti-cancer therapeutics and the other is focused on the development of novel stem cell reagents. My research on cancer, concerns the study of a membrane receptor (MUC1*) that stimulates cancer development. My research also involves the study of ligands that can block the receptor stimulation, the discovery of the signal transduction pathways that are affected by those ligands and the mechanisms that inhibit cancer growth. The receptor in question is present on most cancer cells and constitutes an ideal target for novel cancer therapeutics development. This includes the development of antibodies that block the signal stimulating cancer growth and the use of nanoparticle assays to test small molecule inhibitors developed by chemist at Minerva Biotechnologies. My second research interest in the area of regenerative medicine concerns the development of methods for the culture of human stem cells, in particular, new growth factors that maintain stem cells in a “ground state” that is required for the use of stem cells in human therapies and other medical applications.
Since I began work at Minerva, I have been the lead scientist on projects to develop antibody-based therapeutics that block the cancer-promoting MUC1* activated pathway. I have led multiple aspects of this work including testing of candidate antibodies and small molecules in cell based assays to determine their effects on a large array of cancer cells known to be expressing the MUC1* receptor, including breast cancer cells. Bivalent ligands, including IgGs favor cancer progression by dimerizing and activating MUC1*. Binding of a monovalent ligand, including Fab fragment deactivate the MUC1* receptor and, therefore, inhibit cancer growth. I am the lead scientist responsible for the generation of Fab and had to optimize each step of this complex process for a large scale production and purification of a Fab that is suitable for our assays and for the efficacy and toxicity studies in animal. I have personally tested several Fabs in a cell based assay and isolated candidates having an anti-tumor effect. Both embryonic stem (ES) and induced pluripotent stem (iPS) cells hold great promise for the treatment of a wide variety of acquired or hereditary diseases. The major obstacles to clinical applications are: 1) developing cell culture methods that will comply with expected FDA requirements; 2) culturing enough high quality pluripotent stem cells. In an attempt to create a growth system that enables self-renewal of stem cells, we discovered that NME1 (NM23) can be used as the only growth factor or cytokine required for the culture of human pluripotent stem cells. I am the scientist that discovered how to engineer, express and purify the unique growth factor (NME1) that maintains its oligomerization state as a dimer which is the only active form able to dimerize and activate the membrane receptor MUC1*. NME1 dimers make human stem cells grow in the true pluripotent state called the “naïve” or “ground”state. With my colleagues Andrew Stewart and Mark Carter, who led Minerva’s stem cell team, we showed that human stem cells were converted to, and maintained in, the “naïve” state by culturing the cells in the dimeric form of a NME1. Interestingly, subsequent exposure of the naïve cells to bFGF, the standard growth factor used in all human stem cell culture reversed the process and caused the cells to enter the “primed” state. As predicted by comparison to mouse naive cells, the NME1 cultured stem cells had a much higher cloning efficiency than the same cells cultured in FGF-containing media and differentiated in a coordinated way with as high as 90% of the cells in a local environment differentiating down the same germline. Our growth system, including the NME1 growth factor that I perfected, is free of feeder cells, conditioned media, exogenously added cytokines or growth factors. After initial acclimation to the new media, the stem cells remain essentially 100% pluripotent, requiring no manual dissection or other manipulations that would interfere with large scale production and automated stem cell culture. This important work is the subject of a patent on which I am a co-inventor along with Minerva’s CEO Cynthia Bamdad (Media For Stem Cell Proliferation and Induction, PCT/US12/60684).
The NME1 growth factor described in the 2013 PLoS ONE article and important extensions thereof, constitute an important breakthrough in the human stem cell field as the cells in the naïve state will allow the production of better quality cells for the treatment of incurable diseases, including Alzheimer’s disease, Parkinson’s disease, Spinal cord injury, Heart disease, Stroke, Diabetes, Brain injury, Rheumatoid arthritis, Leukemia and other cancers.