Ph.D., Mayo Graduate School, 2003
Genomic and envrionmental factors in the development of obesity, metabolic syndrome and Type 2 diabetes
According to the Centers for Disease Control and Prevention, the rate of obesity in the United States has doubled since 1990. Today, over sixty percent of the U.S. population is overweight and 30% of adults are categorized as obese, while type II diabetes is the fastest growing non-communicable disease in the U.S. Thus, there is a compelling need to understand and the mechanisms that give rise to and underlie the pathologies associated with excess body weight.
The circadian system is an endogenous timing mechanism that is present across phyla and is responsible for synchronizing an organism's behavior and physiology to the most optimal time of day. In mammals, this system is based on a subcellular transcription-translation circuit which generates strong, ~24-hour oscillations in up to 20% of the transcriptome of any given organ. Thus, the impact of this system is far-reaching, exerting considerable influence and control over most, if not all, major organismal processes. Importantly, the circadian oscillator has emerged as a critical orchestrator of metabolism and energy homeostasis. Consistently, circadian dysfunction due to environmental factors such as those commonly found in modern lifestyles (jet lag, shift work, artificially-extended photoperiod) has been linked to a number of disease processes, including cancer, obesity, and metabolic syndrome.
The overarching goal of my laboratory is to understand how the genome and the environment interact with one another, and the role this interaction plays in human health in general, and in the development of obesity, metabolic syndrome and Type 2 diabetes in particular. Towards this end I aim to:
(1) dissect the genetic programs involved in the maintenance of energy homeostasis of adult, post-differentiated tissues,
(2) understand the molecular mechanisms of the circadian oscillator, and
(3) elucidate how the circadian oscillator and energy metabolism interact with one another and become dysregulated in obesity and disease.
DiTacchio L, Bowles J, Shin S, Lim DS, Koopman P and Janknecht R. (2012) Transcription Factors ER71/ETV2 and SOX9 Participate in a Positive Feedback Loop in Fetal and Adult Mouse Testis. J. Biol Chem. 287(28):23657-66
DiTacchio L*, Vollmers C,*, Hatori M*, Bushong E, Gill S, LaBlanc M, Fitzpatrick J, Ellisman M, and Panda S. (2012) Time-restricted feeding prevents adverse effects of a high-fat diet. Cell Metabolism.15(6):848-60* co-first authorship
Cho H, Zhao X, Hatori M, Yu RT, Barish GD, Lam MT, Chong LW, DiTacchio L,Atkins AR, Glass CK, Liddle C, Auwerx J, Downes M, Panda S, Evans RM. (2012) Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485(7396):123-7
DiTacchio L, Le HD, Vollmers C, Witcher M, Seacombe J and Panda S. (2011) Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock. Science 333, 1881-5.
Jones MA, Covington MF, DiTacchio L, Vollmers C, Panda S, Harmer SL. (2010) Jumonji domain protein JMJD5 functions in both the plant and human circadian systems. Proc Natl Acad Sci U S A. 107(50):21623-8.
Vollmers C, Gill S, DiTacchio L, Pulivarthy SR, Le HD, Panda S. (2009) Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc. Natl. Acad. Sci. USA 106, 21453-8.
Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM. (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326, 437-40.
Hitomi K, DiTacchio L, Arvai AS, Yamamoto J, Kim ST, Todo T, Tainer JA, Iwai S, Panda S, Getzoff ED. (2009) Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes. Proc. Natl. Acad. Sci. USA 106, 6962-7.
DiTacchio L*, Hughes ME*, Hayes KR, Vollmers C, Pulivarthy S, Baggs JE, Panda S, Hogenesch JB. (2009) Harmonics of circadian gene transcription in mammals. PLoS Genet. 5, e1000442. * co-first authorship
Baggs JE, Price TS, DiTacchio L, Panda S, Fitzgerald GA, Hogenesch JB. (2009) Network features of the mammalian circadian clock. PLoS Biol. 7, e52.
Vollmers C, Panda S, DiTacchio L*. (2008) A high-throughput assay for siRNA-based circadian screens in human U2OS cells. PLoS One 3, e3457.*corresponding and co-first authorship
Pulivarthy SR, Tanaka N, Welsh DK, DiTacchio L, Verma IM, Panda S. (2007) Reciprocity between phase shifts and amplitude changes in the mammalian circadian clock. Proc. Natl. Acad. Sci. USA 104, 20356-61.
DiTacchio L, Panda S. (2006) Systems biology of circadian rhythms: an outlook.J. Biol. Rhythms 21, 507-18.
Knebel J*, DiTacchio L*, Janknecht R. (2006) Repression of transcription by TSGA/Jmjd1a, a novel interaction partner of the ETS protein ER71. J Cell Biochem. 99, 319-29.* co-first authorship.
DiTacchio L, Janknecht R. (2005) Cloning of the murine ER71 gene (Etsrp71) and initial characterization of its promoter. Genomics. 85, 493-502.DiTacchio L, Janknecht R. (2002) Functional analysis of the transcription factor ER71 and its activation of the matrix metalloproteinase-1 promoter. Nucleic Acids Res. 30, 2972-9.
Luciano DiTacchio, PhD
4095 HSLIC; MS-1018
3901 Rainbow Blvd.
Kansas City, Kansas 66160
F: (913) 588-7501