Some of my highlights
My laboratory is interested in why and how we age. Specifically, we focus on studying molecular mechanisms of Hutchinson-Gilford progeria syndrome (HGPS), a premature aging disease, and exploring the potential connections between HGPS and normal aging. Children with HGPS die at their early teens due to heart attack or stoke. Approximately 90% of the HGPS cases are causedby a de novo mutation at 1824 position of the lamin A gene (C1824T, G608G). This mutation does not affect the coded amino acid, but partially activates a cryptic splice donor site in the exon 11, leading to the production of a mutant lamin A mRNA that contains an internal deletion of 150 base pairs. This is then translated into a lamin A mutant protein missing 50 amino acids near the C-terminus, termed “progerin”.
- Zhang H, Xiong ZM, Cao K. Mechanisms controlling the smooth muscle cell death in progeria via down-regulation of poly(ADP-ribose) polymerase 1. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):E2261-70. doi: 10.1073/pnas.1320843111. Epub 2014 May 19. PubMed PMID: 24843141; PubMed Central PMCID: PMC4050581.
- Wu D, Flannery AR, Cai H, Ko E, Cao K. Nuclear localization signal deletion mutants of lamin A and progerin reveal insights into lamin A processing and emerin targeting. Nucleus. 2014 Jan-Feb;5(1):66-74. doi: 10.4161/nucl.28068. Epub 2014 Feb 4. PubMed PMID: 24637396; PubMed Central PMCID: PMC4028357.
- Xiong ZM, LaDana C, Wu D, Cao K. An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells. Aging (Albany NY). 2013 Apr;5(4):288-303. PubMed PMID: 23596277; PubMed Central PMCID: PMC3651521.
- McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K. Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res. 2013 Feb;23(2):260-9. doi: 10.1101/gr.138032.112. Epub 2012 Nov 14. PubMed PMID: 23152449; PubMed Central PMCID: PMC3561867.
- Zhang H, Kieckhaefer JE, Cao K. Mouse models of laminopathies. Aging Cell. 2013 Feb;12(1):2-10. doi: 10.1111/acel.12021. Epub 2012 Nov 26. Review. PubMed PMID: 23095062.
- Candia J, Maunu R, Driscoll M, Biancotto A, Dagur P, McCoy JP Jr, Sen HN, Wei L, Maritan A, Cao K, Nussenblatt RB, Banavar JR, Losert W. From cellular characteristics to disease diagnosis: uncovering phenotypes with supercells. PLoS Comput Biol. 2013;9(9):e1003215. doi: 10.1371/journal.pcbi.1003215. Epub 2013 Sep 5. PubMed PMID: 24039568; PubMed Central PMCID: PMC3763994.
- Gordon LB, Cao K, Collins FS. Progeria: translational insights from cell biology. J Cell Biol. 2012 Oct 1;199(1):9-13. doi: 10.1083/jcb.201207072. PubMed PMID: 23027899; PubMed Central PMCID: PMC3461511.
- Driscoll MK, Albanese JL, Xiong ZM, Mailman M, Losert W, Cao K. Automated image analysis of nuclear shape: what can we learn from a prematurely aged cell? Aging (Albany NY). 2012 Feb;4(2):119-32. PubMed PMID: 22354768; PubMed Central PMCID: PMC3314174.
- Graziotto JJ, Cao K, Collins FS, Krainc D. Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders. Autophagy. 2012 Jan;8(1):147-51. doi: 10.4161/auto.8.1.18331. Epub 2012 Jan 1. Review. PubMed PMID: 22170152; PubMed Central PMCID: PMC3336000.
- Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS. Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Invest. 2011 Jul;121(7):2833-44. doi: 10.1172/JCI43578. Epub 2011 Jun 13. PubMed PMID: 21670498; PubMed Central PMCID: PMC3223819.
- Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, Krainc D, Collins FS. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci Transl Med. 2011 Jun 29;3(89):89ra58. doi: 10.1126/scitranslmed.3002346. PubMed PMID: 21715679.
- Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, Gerhard-Herman M, Machan JT, Kutys R, Virmani R, Collins FS, Wight TN, Nabel EG, Gordon LB. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2301-9. doi: 10.1161/ATVBAHA.110.209460. Epub 2010 Aug 26. PubMed PMID: 20798379; PubMed Central PMCID: PMC2965471.
- Capell BC, Olive M, Erdos MR, Cao K, Faddah DA, Tavarez UL, Conneely KN, Qu X, San H, Ganesh SK, Chen X, Avallone H, Kolodgie FD, Virmani R, Nabel EG, Collins FS. A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15902-7. doi: 10.1073/pnas.0807840105. Epub 2008 Oct 6. Erratum in: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13143. PubMed PMID: 18838683; PubMed Central PMCID: PMC2562418.
- Cao K, Capell BC, Erdos MR, Djabali K, Collins FS. A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4949-54. Epub 2007 Mar 14. PubMed PMID: 17360355; PubMed Central PMCID: PMC1821129.
- Vong QP, Cao K, Li HY, Iglesias PA, Zheng Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 2005 Dec 2;310(5753):1499-504. PubMed PMID: 16322459.
- Cao K, Zheng Y. The Cdc48/p97-Ufd1-Npl4 complex: its potential role in coordinating cellular morphogenesis during the M-G1 transition. Cell Cycle. 2004 Apr;3(4):422-4. Epub 2004 Apr 1. PubMed PMID: 15004522.
- Li HY, Cao K, Zheng Y. Ran in the spindle checkpoint: a new function for a versatile GTPase. Trends Cell Biol. 2003 Nov;13(11):553-7. PubMed PMID: 14573347.
- Cao K, Nakajima R, Meyer HH, Zheng Y. The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis. Cell. 2003 Oct 31;115(3):355-67. PubMed PMID: 14636562.
- Tsai MY, Wiese C, Cao K, Martin O, Donovan P, Ruderman J, Prigent C, Zheng Y. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Nat Cell Biol. 2003 Mar;5(3):242-8. PubMed PMID: 12577065.
Kan Cao received the B Sc degree in Biology from the Nanjing University China in 1997, and Ph.D. degree in Biology from the Johns Hopkins University in 2005. She did her postdoctoral fellowship in human genetics and genomics at the National Institutes of Health between 2005-2010. Dr. Cao was named the New Scholar in Aging by the prestigious Ellison Medical Foundation in 2011, received Board of Visitors junior faculty award from the University of Maryland in 2013, and was the finalist of the Invention of the Year by the University of Maryland in 2016. In 2018, she received Norma M. Allewell Prize In Entrepreneurship from the University of Maryland. In 2018, Dr. Cao founded a university startup, Mblue Labs, LLC, which specializes in driving commercialization of the technology and products revolving around MB-based anti-aging applications.
Our Lab Members
During my time there at Penn State, I worked in early-stage drug discovery lab at GlaxoSmithKline, and gained industrial research experience besides academic research, which allowed me to have broader and richer perspectives. My experiences with the diverse research topics triggered my interests in the field of orphan diseases and understanding the molecular mechanisms involved in genetic disorders. I found it meaningful and enjoyable especially when approaching the biological questions in rare diseases, such as HGPS.
One of the characteristics of Hutchinson-Gilford Progeria Syndrome is indicated by skeletal defects in severe loss of bone along with abnormal bone architecture and skeletal fragility. The patients with HGPS have defects in bone differentiation. My project focuses on examining the HGPS-causing mutations on the beta-catenin pathway on Osteoblast differentiation. I am particularly interested in looking at the potential of activated beta-catenin pathway for recovering HGPS defects in bone-forming osteoblasts.
Former Lab Members
- Haoyue Zhang, Postdoctoral fellow at UPenn
- Megan Leung, Executive Administrative Assistant , CBMG, UMD
- Celeste Witting, Medical student at Northwestern Universit
- Melissa Bui Truong, Honors and HHMI Student, now an analyst at Stifel Nicolaus
- Haibei Luo, Ph.D., now a manager at Shanghai Kehua Bio-engineering Co., Ltd., China
- Zeshan Tariq, Honors and HHMI student, now a postbac fellow at NIH/NIAID
- Eunae Ko, FDA fellow
- To-Lam Nguyen, now a medical student at the Univ. of Maryland school of Medicine
- Florian Bigot
- Pratima Bharti, Ph.D., now a Scientist at Stem Cell Technologies, GA
- Jason Albanese, HHMI Student
- Helen Cai, now a proud dental Student at UPenn Dental School
- Julia Kieckhaefer, now a graduate student at UPenn
- Steven Margolis, now a medical student at George Washington Medical school
- Christina LaDana, now a happy nurse at St Joseph Hospital, Baltimore, MD
- Michael O’Donovan, Business Development Manager, MP BIOMEDICALS
- Emily Deboy