Lorenzo Sempere

lorenzo sempere

Dr. Lorenzo Sempere is a tenure-track assistant professor in the Department of Radiology and a faculty member of the campus-wide Precision Health Program at MSU. Dr. Sempere is originally from Elche, a sunny city in southeastern Spain with one of largest palm tree groves in the world. He obtained his B.S. in biochemistry at Universidad Miguel Hernández and trained in the laboratory of Victor Ambros, co-discoverer of microRNAs, at Geisel School of Medicine at Dartmouth College. Dr. Sempere initiated his translational cancer research in the laboratory of Charles Cole with a Susan G. Komen for the Cure postdoctoral fellowship and continued to climb the academic ladder at Dartmouth in the laboratory of Murray Korc with a Laurie and Paul MacCaskill PanCAN-AACR Career Development award. Before joining MSU, Dr. Sempere led his own laboratory research program as research-track faculty first at Geisel School of Medicine and then at Van Andel Research Institute. Dr. Sempere has worked in the field of microRNAs since their discovery in 2001. He has experience and expertise as author, reviewer and journal editor in diverse areas of microRNA research, including evolutionary and developmental biology, molecular and cellular biology, and immunology and cancer biology.

The Sempere Lab

The Sempere Laboratory pursues complementary lines of translational research in cancer prevention and early detection as well as microRNA-based diagnostic and therapeutic applications with a disease focus on breast and pancreatic cancer. The lab uses contextual high-content tissue analyses, 3D modeling, allograft transplantations, genetically engineering animal models and other tools to characterize molecular and cellular tumor heterogeneity and to functionally dissect cancer cell-stroma interactions as well as to identify microRNA-regulated gene networks in development (organ formation), physiology and disease (cancer initiation and progression).

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Research Program

These are the three main research lines in the Sempere Lab and specific projects and question of interest within each research lines. We are currently investigating some of the questions, but others need talented individuals to lead the discovery efforts. Please contact Dr. Sempere if you are interested in learning more about a particular research project.

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Cancer prevention and early detection

Intraductal ablation for primary prevention of breast cancer:

  • Pre-clinical studies: mouse and rat models for chemical and thermal ablation.
  • 3D human models, large animal models and first-in-human trials.

Exosomal microRNA signatures of malignancy in breast cancer:

  • Pre-clinical trial: serum and tissue correlative studies in patient-derived xenograft models
  • Clinical trial: serum and tissue correlative studies.

Diabetes type 3C: cause or consequence of pancreatic cancer:

  • Pre-clinical studies: monitor diabetes, cancer-induced diabetes in K-Ras driven animal models.
  • Clinical trial: non-invasive monitoring of glucose levels in at-risk individual of developing pancreatic cancer for early detection.
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Integrated and interventional microRNA biomarkers

Cell type-specific roles of microRNAs activity in breast cancer:

  • Pre-clinical: genetic and pharmacological approaches to study microRNA activity in animal models of triple-negative breast cancer.
  • Clinical trial: stromal microRNA expression-driven signature for treatment selection in triple-negative breast cancer cases.

Role of cell type-specific microRNA activity in animal models of pancreatic cancer:

  • Pre-clinical studies: genetic and pharmacological approaches to study activity of selected microRNAs in K-Ras-driven animals models of pancreatic cancer.
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Generation of large animal models for cancer and organ transplant research

CRISPR-engineered rat and pig K-Ras driven cancer models:

  • Conditional Cre/LoxP for inducible cancer in target organ by local delivery of Adeno-Cre (e.g., breast, lung, pancreas, ovary, colon).
  • In vivo imaging and monitoring of RNA-based therapeutics.
  • Targeted delivery and large scale-enzymatic production of microRNA activity modulators.

CRISPR-engineered mouse and pig host for interspecies blastocyst-stage transplantation/complementation for xenogenic organ production:

  • Develop genetic tools for dominant master gene promoter- mediated deletion of host cells to enrich donor contribution to parenchyma of targeted organ by blastocyst complementation.
  • Develop genetic tools for recessive microRNA regulatory binding-mediated deletion of host stroma to enrich donor contribution to stroma of targeted organ by intrinsic processes of developmental commitment and differentiation.

    

Research Funding

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Selected publications

Cancer

Sempere LF, Keto J, Fabbri M. 2017. Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications. Cancers (Basel). Jun 24;9(7):71.   PubMed

Andrew AS, Marsit CJ, Schned AR, Seigne JD, Kelsey KT, Cowper R, Moore JH, Perreard J, Karagas MR, Sempere LF. 2015. Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence. Int J Cancer. Sep 1;137(5):1158-66.    PubMed    Article

Graveel CR, Calderone HM, Westerhuis J, Winn ME, Sempere LF. 2015. Critical analysis of the potential for microRNA biomarkers in breast cancer management. Breast Cancer (Dove Med Press). 7:59–79.     Article      Video abstract

MacKenzie TA, Schwartz G, Calderone HM, Graveel CR, Winn ME, Hostetter G, Wells WA, Sempere LF. Stromal expression of miR-21 identifies high-risk group in triple-negative breast cancer. Am J Pathol. 184(12): 3217–3225. PubMed

Cubillos-Ruiz JR, Baird JR, Tesone AJ, Rutkowski MR, Scarlett UK, Camposeco-Jacobs AL, Anadon-Arnillas J, Harwood NM, Korc M, Fiering SN, Sempere LF, Conejo-Garcia JR. 2012. Reprogramming tumor-associated dendritic cells in vivo using microRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res. 72(7):1683-93. PubMed

Preis M, Gardner TB, Gordon SR, Pipas MJ, Mackenzie TA, Klein EE, Longnecker DS, Gutmann EJ, Sempere LF, Korc M. 2011. microRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin Cancer Res. 17(17):5812-21. PubMed

Sempere LF, Preis M, Yezefski T, Ouyang H, Suriawinata AA, Silahtaroglu A, Conejo-Garcia JR, Kauppinen S, Wells W, Korc M. 2010. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered microRNA expression in solid tumors. Clin Cancer Res. 16, 4246-4255. PubMed 

Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, Wells W, Kauppinen S, Cole CN. 2007. Altered microRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res. 67(24):11612-20. PubMed

Evo/Devo

Fromm B, Tyler BJ, Morten J, Peck LE, Tarver JE, King BL, Newcomb JM, Sempere LF, Flatmark K, Hovig E, Peterson KJ. 2015 A uniform system for the annotation of human microRNA genes and the evolution of the human microRNAome. Annu Rev Gen. 49(1):213–242. Article

Machiela E, Popkie A, Sempere LF. 2015. Individual noncoding RNA variations: Their role in shaping and maintaining the epigenetic landscape In: Trygve Tollefsbol, ed.  Waltham, Massachusetts: Academic Press 2015. Chapter 4 pages:84-114. ISBN-13: 978-0124201354

Heimberg AM, Sempere LF, Moy VN, Donoghue PC, Peterson KJ. 2008. MicroRNAs and the advent of vertebrate morphological complexity. Proc Natl Acad Sci U S A. 105(8):2946-50. PubMed

Sempere LF, Cole CN, McPeek MA, Peterson KJ. 2006. The phylogenetic distribution of metazoan microRNAs: Insights into evolutionary complexity and constraint. J Exp Zool (Mol Dev Evol). 306B:575-588. PubMed

Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. 2004. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 5, R13. PubMed

Sempere LF, Sokol NS, Dubrovsky EB, Berger EM, Ambros V. 2003. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-complex gene activity. Dev Biol. 259(1):9-18. PubMed

Sempere LF, Dubrovsky EB, Dubrovskaya VA, Berger EM, Ambros V. 2002. The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogasterDev Biol.  244(1):170–179.  PubMed


Contact information:
517-355-3982
semperel@msu.edu