Matthew Ishahak, PhD (2020-2022)

The legacy of Rita Levi-Montalcini has had a profound impact on my career. Like Dr. Levi-Montalcini, I found my way to St. Louis to pursue research under a mentor whose work I greatly admired. Also, having started my postdoctoral fellowship during the COVID-19 pandemic, both Dr. Levi-Montalcini and I found ourselves trying to conduct research under unique conditions. Beyond research, Dr. Levi-Montalcini’s legacy has also inspired me to be active in scientific advocacy. In the upcoming year, I will be serving on the Center of Regenerative Medicine Early Career Executive Council. I have also been an active mentor for trainees in the Millman Lab.

As a Rita Levi-Montalcini Postdoctoral Fellow, my research has focused on engineering models of human development and disease using stem cell-derived organoids and single-cell sequencing technologies. In the Millman Lab, I primarily study stem cell-derived islets (SC-islets). Epigenetics and gene expression play and important role in developmental biology and stem cell differentiation, however there has been little significant biological relevance applied within the context of SC-islet development and maturation. Over the last year, most of my effort has focused on filling this gap in knowledge. To achieve this, I have developed a multiomic roadmap of SC-islet differentiation by simultaneously sequencing the chromatin accessibility and gene expression from 57,613 across 8 time points during our differentiation protocol. Using a custom-built bioinformatics toolbox, I am defining cell-specific gene regulatory networks and performing simulations to identify novel transcription factors that regulate cell fate. This project is funded by an award from the Human Islet Research Network (HIRN) “Catalyst” initiative based on a proposal I developed. I am also working on a project in collaboration with a lab at Boston Children’s Hospital to develop SC-islets with a functional vascular network. This work, funded by a grant from the Juvenile Diabetes Research Foundation, will hopefully lead to vascularized SC-islets that survive and function better when transplanted into patients with diabetes.

In addition to work with SC-islets, I have also been developing a model of glioblastoma using genetically engineered stem cells. This project, in collaboration with Dr. Albert Kim’s lab in the Department of Neurological Surgery, aims to understand how specific mutations found in glioblastoma lead to the formation of tumors. To achieve this, we genetically engineered stem cells to harbor glioblastoma-specific mutations, differentiated these stem cells into neural stem cells, and then transplanted them into mice. Using single-cell RNA sequencing, we characterized the gene expression from neural stem cells before transplantation and the tumors they formed after transplantation to identify potential genes that regulate tumor formation. I also performed single-cell RNA sequencing on brain organoids generated from the genetically engineered stem cells. This analysis aims to better understand how glioblastoma-specific mutations hijack neural development mechanisms to drive tumor formation.

Over the past year, I have presented my work at multiple international conferences and seminar series both within Washington University and in the broader research community. I shared my glioblastoma organoid work as a poster at the 2022 International Society for Stem Cell Research Annual Meeting and as an oral presentation at the 2022 Biomedical Engineering Society Annual Meeting. In August 2022, I presented my research in the BME Underrepresented Needs in Technology and Engineering Seminar Series. In April 2023, I will be presenting both my SC-islet and glioblastoma organoid projects as separate Rapid Fire oral presentations at the 2023 TERMIS-AM Conference in Boston. I have also provided regular updates on my research at the Joint Islet Research Group, NeuroRestorative Group, and Single Cell Group meetings at Washington University. My efforts have led to authorship on three peer-reviewed articles which are currently under review and expected to be published this year in Nature Cell Biology, Journal of Visualized Experiments, and Cell Stem Cell.

Mohamed G. Hassan, BDS, MSc, PhD (2021-2023)

I am an Egyptian Orthodontist-Scientist with a long-term goal of innovating within Orthodontics and Dentofacial Orthopaedics by applying data gathered from basic and clinical research to understand the mechanisms regulating craniofacial morphogenesis and multi-interface tissue regeneration. For the international research community, Rita Levi-Montalcini remains an inspiring free thinker and an icon of perseverance for young researchers worldwide. As a young girl, she decided to become a doctor, against her family’s wishes. Many years later, she demonstrated she was a free thinker upon leaving Italy alone to continue her research here at Washington University in St. Louis. Inspired by her legacy and following her steps, I believe that the Rita Levi Montalcini Postdoctoral Fellowship substantially contributed to my development as an independent researcher, promoting novel approaches to bridge cellular and physiological processes in craniofacial tissue regeneration.

As a postdoctoral fellow in the Scheller Lab, I am interested in studying craniofacial skeletal regeneration. Unlike long bones, craniofacial bones are derived from two different embryonic origins; neural crest and mesoderm. Previously, neural crest-derived frontal bone has shown a greater proliferative and osteogenic potential than mesoderm-derived parietal bone. However, the fundamental molecular and cellular mechanisms underlying this result remain unclear. In the Scheller lab, we identified a novel periosteal p75-NTR+ cell population that may contribute to the enhanced regeneration capacity of the neural crest-drived bone. Besides working on enhancing craniofacial skeletal regeneration, we were interested in investigating how environmental conditions like diet can reprogram craniofacial skeletal development and induce trans- and intergenerational effects on offspring craniofacial morphology. Our preliminary results support the idea that maternal diet impairs offspring craniofacial morphology and highlight the implications for understanding one possible pathway for environment-triggered skeletal malocclusions. In addition, such findings should highlight the role of environmental and epigenetic stimuli as factors in the etiology of skeletal malocclusion.

During the last year, I had the opportunity to present the findings of our projects on different occasions including the Rita-Levi Montalcini Symposium of Regenerative Medicine and the Annual Meeting of the American Society for Bone and Mineral Research (ASBMR). In addition, I published and co-authored 3 articles in peer-reviewed journals (Hassan et al 2022 Orthod Craniofac Res, Hankeova et al 2022 EMBO Mol Med, Chen et al 2022 JBMR Plus), and I have been awarded the Rita Levi-Montalcini Prize for the best poster presented during 2022 WUSTL Developmental Biology retreat. In addition, I was offered a scholarship to attend the Faculty Career Enrichment (FaCE of Orthodontics) Faculty Development Workshop during the Consortium for Orthodontic Advances in Science and Technology (COAST).

Regarding career development, I have been selected to serve as a member of the Early Investigator Committee of different institutions and organizations including the WUSTL Center of Regenerative Medicine, and the International Society of Bone Morphometry (ISBM). Inspired by how Dr. Montalcini was supporting the young members of her research team, my goal in joining these committees is to raise awareness of the challenges that might impact early-career scientists and provide novel modalities that can help and support them career-wise and personally.

Sade Williams Clayton, PhD (2021-2023)

My postdoctoral work aims to discover the essential cells and molecular signals that govern healing and repair of the spinal column after injury. The spinal column is an invaluable structure of the musculoskeletal system and the defining characteristic of vertebrate animals. Spinal columns function to provide continued bodily support over an entire lifespan, and therefore naturally sustain aging-related injuries overtime. An essential component of the spinal column is the intervertebral disc (IVD), a connective tissue that provides the weight distribution properties of the spine. IVDs are complex, heterogeneous structures that are prone to degeneration as we age and thus difficult to repair after injury. The accrual of IVD injuries is associated with debilitating pain, leading to a reduction in quality of life. Successful healing of connective tissues relies on temporally regulated immune cells that rapidly migrate into damaged tissues and initiate healing after injury. However, the identity of these immune cell subtypes, their temporal coordination, and their effect on the activation of regenerative signaling pathways following IVD injury remain understudied. The objective of my postdoctoral studies is to define the role of the immune system in IVD healing and identify the relationship between inflammation and repair pathways using rodent models to reduce the burden of spine-related pain as we age.

Since starting my post-doctoral training in the laboratories of Dr. Simon Tang and Dr. Lori Setton on September 1, 2021, I have made great strides in addressing the objectives of my work. By using methodologies like quantitative polymerase chain reaction, single cell RNA sequencing, flow cytometry, and histology, I have begun to unravel the complex relationship that the immune system has with IVD tissues and identify ways that the musculoskeletal field can harness this relationship to improve healing. I have been selected to give four podium presentations at national and international conferences to share my work, and I won two podium presentation awards for my efforts. These conferences include: 2023 Gordon Cartilage and Pathobiology Conference in Tuscany, Italy, 2023 Orthopaedic Research Society (ORS) Annual Meeting in Dallas, TX, the Rita Levi-Montalcini Regenerative Medicine Symposium at Washington University, and the ORS Philadelphia Spine Research Symposium (PSRS) 6th International Spine Symposium at Skytop, PA. I have also been invited to give two poster presentations at the 2022 ORS Annual Meeting in Tampa, FL and the 2022 Musculoskeletal Biology and Regeneration Meeting at Washington University, and won poster presentation awards for both. Most excitingly, I was selected as an awardee of the prestigious 2023 New Investigator Recognition Award (NIRA) Awardee during the 2023 ORS Annual Meeting for the impact my work is making the musculoskeletal field. These efforts have led to two publications in Preprints and Applied Sciences.

I have also been very active in non-academic roles such as mentoring, teaching, outreach and service activities. I have trained two Washington University undergraduate students on laboratory techniques and one will be a coauthor on my upcoming manuscript. I have served as a lecturer in a Cell Biology course at Southern Oregon University to teach on the subject of Stem Cells and Tissue Renewal. Also, I have created and implemented four hands-on outreach workshops to teach middle and high school students about spine biology. To sharpen my skills as a mentor and lecturer, I completed the Leadership and Management in Action Program (LMAP) and LMAP Facilitator courses offered at Washington University in the spring 2022 and spring 2023 semesters, respectively. To increase Diversity, Equity and Inclusion at Washington University, I created the Washington University in St. Louis Black Postdoctoral Association (WUSTLBPA) and helped establish a postdoctoral award to honor diverse postdocs who excel in scholarly activities that is named after a famous St. Louis native, Dr. Maya Angelou. The award is a part of the James E. McLeod Awards and is named the Maya Angelou Award. To continue the progress I have made in my work, I will publish my first, first author manuscript on my work by the end of the summer 2023 and begin work on my second, first author publication simultaneously. I plan to have the second manuscript published by the summer of 2024. I will also attend at least two more conferences in 2023 to share my work with the musculoskeletal biology field.