Rong Lu, PhD
Assistant Professor of Stem Cell Biology and Regenerative Medicine
Office Phone: 323-442-0169
Lab Phone: 323-442-0182
Office Location: 1425 San Pablo St., BCC 306
Lab Location: 1425 San Pablo St., BCC 305
- Postdoctoral Scholar, Stanford University, 2007–2013
- PhD, Princeton University, 2002–2007
- B.S., Lanzhou University, China PR, 1997–2001
Lu R, Neff NF, Quake SR, Weissman IL. Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding. Nature Biotechnology. 2011 Oct 2;29(10):928–33. doi: 10.1038/nbt.1977. PMID: 21964413. [PubMed]
Lu R, Markowetz F, Unwin RD, Leek JT, Airoldi EM, Boyer LA, Troyanskaya OG, Whetton AD, Lemischka IR. Systems-level dynamic analyses of fate change in murine embryonic stem cells. Nature. 2009 Nov 19;462(7271):358–62. doi:10.1038/nature08575. PMID: 19924215. [PubMed]
Wu AR, Hiatt JB, Lu R, Attema JL, Lobo NA, Weissman IL, Clarke MF, Quake SR. Automated microfluidic chromatin immunoprecipitation from 2,000 cells. Lab on a Chip. 2009 May 21;9(10):1365–70. doi: 10.1039/b819648f. PMID: 19417902. [PubMed]
Guan Y, Myers CL, Lu R, Lemischka IR, Bult CJ, Troyanskaya OG. A genomewide functional network for the laboratory mouse. PLOS Computational Biology. 2008 Sep 26;4(9):e1000165. doi: 10.1371/journal.pcbi.1000165. PMID: 18818725. [PubMed]
Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, Decoste C, Schafer X, Lun Y, Lemischka IR. Dissecting self-renewal in stem cells with RNA interference. Nature. 2006 Aug 3;442(7102):533–8. doi:10.1038/nature04915. PMID: 16767105. [PubMed]
Complete PubMed List
Our lab studies stem cell regulatory mechanisms at the single cell level. Stem cells are responsible for maintaining tissue homeostasis and for repairing tissue after injury. Their regenerative capacity possesses enormous therapeutic potential. Regeneration is a concerted effort involving multiple stem cells. While individual stem cells may be differentially regulated, their overall activities must be strictly coordinated to ensure proper tissue size and function.
Stem cell coordination and regulation are particularly challenging for tissues with fast cellular turnover, such as blood. In an adult human, tens of thousands of hematopoietic stem cells (HSCs) produce more than 100 billion blood cells every day. Blood can be easily sampled, and its circulation ensures that the sampling faithfully represents the contributions of all stem cells. These unique characteristics make HSCs an optimal model for studying stem cell coordination and regulation.
In addition to their scientific significance, HSC studies also possess immediate clinical impact. HSCs play a pivotal role in bone marrow transplantation, the earliest and by far the most prevalent stem cell therapy. However, bone marrow transplantation remains a risky procedure reserved only for patients with life-threatening diseases. A better understanding of HSC regulation is crucial for improving the safety and efficacy of this treatment and for adapting it to meet patient-specific requirements.
Our recent studies show that HSC coordination is substantially altered by the conditioning regimen accompanying the transplantation. (See figure.) If a recipient is treated with conditioning such as irradiation prior to transplantation, individual HSCs produce distinct numbers of blood cells and differentially supply different cell types. This HSC coordination pattern persists throughout the recipient’s lifetime. In contrast, in the absence of pre-transplantation conditioning, individual HSCs uniformly supply the blood. We have also found that changes to HSC coordination are not stochastic, but instead are rigorously regulated at distinct steps of HSC differentiation. These findings reveal new mechanisms of stem cell regulation that are undetectable at the population level.
Our current studies are driven by three major questions. (1) How are individual HSCs regulated to produce different amounts and types of blood cells? (2) How are distinct HSCs coordinated to ensure an overall balanced blood supply? (3) How does miscommunication between stem cells cause diseases?
To address these questions in vivo, we use mouse HSCs as a model system. Our multidisciplinary group specializes in single cell analysis that integrates research strategies from molecular biology, cell biology, systems biology, genetics, and bioinformatics. Our goal is to understand stem cell regulation, coordination, and malfunction at cellular and molecular levels. These studies are not only essential for understanding stem cell biology, but they will also provide new insights into the origins of many diseases and will help to identify new therapeutic targets.