School of Medicine
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Hiromitsu (Hiro) Nakauchi
Professor of Genetics (Stem Cell)
Current Research and Scholarly Interests Translation of discoveries in basic research into practical medical applications
Postdoctoral Research Fellow, Stem Cell Biology and Regenerative Medicine
Current Research and Scholarly Interests My MSc project, carried out at the University of Salzburg in cooperation with the biotechnology company ProComCure, investigated the molecular interface between human cells and the bacterium Staphylococcus aureus. S. aureus exhibits a dramatic increase in resistance to antibiotics, thereby causing enormous challenges for health care. Using proteomics platforms, I identified numerous novel host-pathogen interactions. These findings are being developed further by ProComCure in order to design innovative therapies for S. aureus infections.
My dissertation project, carried out at the University of Calgary, defined the functions of the human protein TPX2. TPX2 has been discovered over 17 years ago for its unique property to mediate cell division. However, when not involved in cell division TPX2 resides in the cell nucleus where its role had remained unknown. Building on my background in proteomics, I discovered a novel TPX2-containing protein complex that resides in the nucleus. Analysis of this complex unraveled a completely unexpected role for TPX2 in cellular reactions triggered by insults to DNA. To avoid cancers, cells respond to damaged DNA by either attempting its repair or, if this is not possible, by committing 'suicide'. My findings established that TPX2 impacts the molecular mechanisms that underlie these responses to DNA damage. More specifically, I found that TPX2 accumulates at DNA lesions and that the cellular levels of TPX2 negatively correlate with the ‘strength’ of the DNA damage response. Thus, TPX2 affects cellular proliferation, DNA repair, and survival upon genomic insult. This was the first function discovered for TPX2 in the cell nucleus. Since abnormally high levels of TPX2 are often found in human cancers, my discovery sheds light on the mechanistic implication of this protein in carcinogenesis. Furthermore, TPX2 is also a promising therapeutic target and my findings may advance novel cancer therapies. We propose that future treatments may attempt to reduce TPX2 levels in order to increase the strength of the DNA damage response. Subsequently, chemo- and radiotherapy doses may be lowered but still stay effective.
In 2014, I joined the Wernig laboratory at Stanford University. Here, I capitalize on my expertise in mechanisms of DNA damage response to develop a pioneering technique capable of repairing pathogenic mutations in the genetic material of patients suffering from Epidermolysis Bullosa (a devastating and often lethal disease that causes chronic erosion of the skin). This novel technique, called CRISPR, introduces experimentally controlled and transient damage to the mutated DNA of patient cells and exploits naturally occurring DNA repair mechanisms to transform the disease-causing mutation to a normal state. I will combine development of CRISPR with Dr. Wernig’s expertise in regenerative medicine to generate patient derived stem cells with repaired (i.e. normal) genes. Subsequently, these stem cells will be employed to regenerate the skin of Epidermolysis Bullosa patients.
Assistant Professor of Biomedical Data Science
Current Research and Scholarly Interests Our group focuses on building novel data science tools to better understand the cellular and molecular composition of normal and neoplastic tissues. We are using these tools, together with high throughput sequencing, single cell genomics, and experimental techniques, to study the diversity and clinical significance of (i) cancer cell subtypes involved in tumor initiation, maintenance, and metastasis, and (ii) stromal cell subsets in the tumor microenvironment.
Virginia and Daniel K. Ludwig Professor in Cancer Research and the Reed-Hodgson Professor in Human Biology
Current Research and Scholarly Interests Our laboratory studies Wnt signaling in development and disease. We found recently that Wnt proteins are unusual growth factors, because they are lipid-modified. We discovered that Wnt proteins promote the proliferation of stem cells of various origins. Current work is directed at understanding the function of the lipid on the Wnt, using Wnt proteins as factors the expand stem cells and on understanding Wnt signaling during repair and regeneration after tissue injury.