Federico Innocenti Lab

 

Professor Innocenti’s NIH-funded program applies genomic technologies to discover novel determinants of efficacy and safety of cancer therapy. This research aims to achieve the goal of precision therapy in oncology through the selection of the most effective treatment regimen for any given patient.

The program is structured in three main themes:

  • Theme 1: Genomic studies in patients with gastrointestinal tumors. Genomic data are obtained from patients enrolled in clinical trials of novel therapies using next-generation sequencing of DNA (tumor and germline) and RNA (tumor). Genomic profiling of the patient and the tumor will predict the outcome of patient survival and the side effects of therapy.
  • Theme 2: Genome-wide regulation of gene expression. Elucidating the genetic basis of differences in gene expression in the human liver is instrumental to discover new heritable determinants of liver-mediated response to medications.
  • Theme 3: Functional analysis of novel gene variants. The results of both Themes 1 and 2 provide a large series of new genetic variants for functional validation. The laboratory employs various cell-based assays to test the function of new genetic variants to provide mechanistic foundations.

 

For a complete list of publications, please click here

Exemplary Publications from the last 5 years:

  1. A New Liver Expression Quantitative Trait Locus Map From 1,183 Individuals Provides Evidence for Novel Expression Quantitative Trait Loci of Drug Response, Metabolic, and Sex-Biased Phenotypes. Etheridge AS, Gallins PJ, Jima D, Broadaway KA, Ratain MJ, Schuetz E, Schadt E, Schroder A, Molony C, Zhou Y, Mohlke KL, Wright FA, Innocenti F. Clin Pharmacol Ther. 2019 Dec 23. doi: 10.1002/cpt.1751. [Epub ahead of print] PMID: 31868224
  2. Mutational Analysis of Patients With Colorectal Cancer in CALGB/SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome. Innocenti F, Ou FS, Qu X, Zemla TJ, Niedzwiecki D, Tam R, Mahajan S, Goldberg RM, Bertagnolli MM, Blanke CD, Sanoff H, Atkins J, Polite B, Venook AP, Lenz HJ, Kabbarah O. J Clin Oncol. 2019 May 10;37(14):1217-1227. doi: 10.1200/JCO.18.01798. Epub 2019 Mar 13. PMID: 30865548
  3. Genetic variation determines VEGF-A plasma levels in cancer patients. Innocenti F, Jiang C, Sibley AB, Etheridge AS, Hatch AJ, Denning S, Niedzwiecki D, Shterev ID, Lin J, Furukawa Y, Kubo M, Kindler HL, Auman JT, Venook AP, Hurwitz HI, McLeod HL, Ratain MJ, Gordan R, Nixon AB, Owzar K. Sci Rep. 2018 Nov 5;8(1):16332. doi: 10.1038/s41598-018-34506-4. PMID: 30397360
  4. Genetic Variants of VEGFA and FLT4 Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib. Crona DJ, Skol AD, Leppänen VM, Glubb DM, Etheridge AS, Hilliard E, Peña CE, Peterson YK, Klauber-DeMore N, Alitalo KK, Innocenti F. Cancer Res. 2019 Jan 1;79(1):231-241. doi: 10.1158/0008-5472.CAN-18-1089. Epub 2018 Nov 1. PMID: 30385613
  5. The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation. Innocenti F, Owzar K, Jiang C, Etheridge AS, Gordân R, Sibley AB, Mulkey F, Niedzwiecki D, Glubb D, Neel N, Talamonti MS, Bentrem DJ, Seiser E, Yeh JJ, Van Loon K, McLeod H, Ratain MJ, Kindler HL, Venook AP, Nakamura Y, Kubo M, Petersen GM, Bamlet WR, McWilliams RR. PLoS One. 2018 Aug 14;13(8):e0202272. doi: 10.1371/journal.pone.0202272. eCollection 2018. PMID: 30107003
  6. Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel-Hypermutated Cancer Genome and Comutation of POLD1 and MLH1. Sharma MR, Auman JT, Patel NM, Grilley-Olson JE, Zhao X, Moschos SJ, Parker JS, Yin X, Hayward MC, Polite BN, Marangon E, Posocco B, Toffoli G, Hayes DN, Innocenti F. JCO Precis Oncol. 2017;2017. doi: 10.1200/PO.16.00015. Epub 2017 Apr 27. PMID: 30009279
  7. Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer. Toffoli G, Sharma MR, Marangon E, Posocco B, Gray E, Mai Q, Buonadonna A, Polite BN, Miolo G, Tabaro G, Innocenti F. Clin Cancer Res. 2017 Feb 15;23(4):918-924. doi: 10.1158/1078-0432.CCR-16-1012. Epub 2016 Aug 9. PMID: 27507617
  8. Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance). Niedzwiecki D, Frankel WL, Venook AP, Ye X, Friedman PN, Goldberg RM, Mayer RJ, Colacchio TA, Mulligan JM, Davison TS, O’Brien E, Kerr P, Johnston PG, Kennedy RD, Harkin DP, Schilsky RL, Bertagnolli MM, Warren RS, Innocenti F. J Clin Oncol. 2016 Sep 1;34(25):3047-53. doi: 10.1200/JCO.2015.65.4699. Epub 2016 Jul 18. PMID: 27432924
  9. Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. Innocenti F, Schilsky RL, Ramírez J, Janisch L, Undevia S, House LK, Das S, Wu K, Turcich M, Marsh R, Karrison T, Maitland ML, Salgia R, Ratain MJ. J Clin Oncol. 2014 Aug 1;32(22):2328-34. doi: 10.1200/JCO.2014.55.2307. Epub 2014 Jun 23. PMID: 24958824

Dr. Innocenti’s CV

Professor Innocenti’s research focuses on the discovery of effective strategies for individualizing therapy for cancer patients through the identification of heritable (in the patient) and acquired (in the tumor) genetic determinants of therapeutic outcome, both in the laboratory and the clinic.

Federico Innocenti

(919) 966-9422

innocent@email.unc.edu

Dr. Innocenti’s NIH-funded research program is currently focused on the discovery of genomic determinants of efficacy and toxicity of cancer chemotherapy, integrating clinical genomic investigation with functional evaluation of gene variation.

Kelli Hammond

(919) 966-9183

hammondk@email.unc.edu

The Innocenti lab works with data and specimens from many clinical trials. Kelli is the translation research coordinator for the lab which involves project planning, organizing team conference calls, as well as sample and data management. hammondk@email.unc.edu

Spinel Karas

spin@email.unc.edu

Spinel Karas, PharmD, is a graduate student in the Division of Pharmacotherapy and Experimental Therapeutics. Spinel’s research interests include population pharmacokinetic/pharmacodynamic modeling and genome-wide analyses of chemotherapeutic drug disposition and toxicities in cancer patients.

Sarah Catherine Mills – Research Intern

Alessandro Racioppi – Research Intern

Evangelia Tsermpini – University of Patras, Greece

Daniel Crona – Assistant Professor, UNC Eshelman School of Pharmacy