After studying tons of research papers and procedures, exchanging with Dr. Jiang in one-on-one meetings, and attending a series of presentations, demos, and virtual tours by Cedars-Sinai experts, two key success factors for cutting-edge research stand out to me at this point: 1) interlinked, multidisciplinary approaches, and 2) state-of-the-art resources.
1) While our lab aims to develop stem cell-directed therapies for back pain resulting from intervertebral disc (IVD) degeneration, we face a huge puzzle which requires tackling lots of different pieces and interdependencies, and then drilling down deep into one bit at a time. My own path to absorbing knowledge in this field led me from stem cell basics and reprogramming, back to the biology of our target, namely the physiology and morphology of healthy intervertebral disc (IVD) cells, that is nucleus pulposus (NP) and annulus fibrosus (AF) cells. Then, I moved to degeneration characteristics, and eventually to the complexity of causes. Beside natural aging (senescence) and environmental factors, the current understanding is that IVD degeneration is influenced by genetic factors, many of which are unknown. So, while Dr. Sheyn has established the utility of human iPSCs for reducing degenerated IVD tissue in vivo in a previous study using a porcine model, our lab currently focuses on the genetic disposition to develop IVD degeneration, with an emphasis on the role of pain. We are undertaking a study supported by next generation sequencing (NGS) of relevant human patient samples that investigates genetic expressions. Based on this research direction, my learning has transitioned into genomics, currently studying up on genes mostly associated with IVD degeneration, such as Collagen. It was very interesting when Dr. Jiang showed me steps of analysis of the performed single-cell RNA sequencing (scRNA-seq). The gene expression profiling of NP cells he shared illustrated molecular signatures in differentiated expression clusters segmented by the phenotypes we are looking into (healthy, degeneration with pain, and asymptomatic degeneration). The next step for me is to analyze and establish connections of a set of identified expressed genes. Overall, the Sheyn Lab’s work showed me that many disciplines, such as (stem and somatic) cell biology, molecular biology (specifically genomics), bioinformatics, and biophysics need to come together to advance the research.
2) The tours through Cedars-Sinai research facilities our intern group was invited to attend this week, specifically, the Vivarium and the Research Imaging Center, were impressive and showed me how important these resources are to be able to conduct leading research. I was surprised to see how large the Vivarium was, with many species-specific rooms holding animals, ranging from small rodents to large animals. Although the thought of sacrifice is not easy to accept, in vivo animal models are an essential step on the way to human clinical trials. Cedars-Sinai takes the ethical responsibilities with maintaining an appropriate environment and quality veterinary care for the animals very seriously, and I was relieved to hear that the dogs get released and adopted after having served in research. When Dr. Tawackoli led us through the imaging center, I was extremely impressed. This truly is an excellent facility, which has all the newest imaging technology and instrumentation for both, human and animal studies. The instrumentation we have seen included human MRI systems, such as the Siemens Magnetom Vida 3T, small animal MRI, such as the Bruker BioSpin 9.4T, CT scanner, Optical Imaging, Fluorescence Microscopy, and X-Ray. It was particular intriguing to observe an imaging process of a pig for a heart study in the Siemens Biograph mMR PET-MRI machine, which is one of the newest, most advanced diagnostic tools. The astronomical cost for all this technology, for example about $8 million for the PET-MRI, explains why research grants are so highly selective.
RMI CIRM SPARK 