Christopher Vulpe

Christopher Vulpe, MD, PhD

Professor

Department: Department of Physiological Sciences
Business Phone: (650) 291-5679
Business Email: cvulpe@ufl.edu

Research Profile

Ecotoxicology

We are developing novel approaches for identifying and understanding the toxicity of chemicals and nanomaterials in aquatic ecosystems. We are focused on the aquatic indicator species Daphnia magna (a crustacean) as well as representative fish species such as Rainbow Trout. We haveMost recently, we are focused on developing a mechanistic understanding the effects of silver nanowires in these species. We are also developing CRISPR based approaches to assess the function of toxicant related genes.

Genetics of Iron Homeostasis

Genetic variants influence iron homeostasis in mammals. My group has utilized genome wide approaches to identify genetic factors that influence iron status in mammals. Recently, we performed an association analysis of over 100 inbred strains of mice to identify genetic determinants of iron status in collaboration with Jake Lusis and Eleazar Eskin at UCLA. Ongoing work is to determine the functional role of candidate genes identified in these studies.

Mammalian ferroxidases – Hephaestin

Intestinal iron absorption is remarkably balanced to provide adequate iron to meet the body’s iron needs while preventing toxic excess. In a collaboration with Greg Anderson from QIMR, Brisbane Australia, Hephaestin (Hp) was identified to be a membrane-bound copper containing ferrroxidase required for export of iron from the intestinal enterocyte into the circulation. We have utilized floxed Hephaestin (Heph) to generate both complete and tissue specific knockouts confirming that global and intestinal specific knockouts result in systemic iron deficiency. Furthermore, we have developed mice which lack both Hephaestin and Ceruloplasmin, the circulating ferroxidase, which develop a much more severe phenotype of iron deficiency than either alone and provide compelling evidence for complementary and partially compensatory functions. In collaboration with Huijun Chen, at Nanjing University, we have demonstrated increased iron levels in many regions of the brain in mice lacking the Heph gene. Most recently, we have been analyzing the molecular mechanisms of the hairloss phenotype associated with iron deficiency in Heph KO mice.

Open Researcher and Contributor ID (ORCID)

0000-0001-5134-8929

Publications

2021
Applying genome-wide CRISPR to identify known and novel genes and pathways that modulate formaldehyde toxicity.
Chemosphere. 269 [DOI] 10.1016/j.chemosphere.2020.128701. [PMID] 33189395.
2020
Genetic screens reveal CCDC115 as a modulator of erythroid iron and heme trafficking.
American journal of hematology. 95(9):1085-1098 [DOI] 10.1002/ajh.25899. [PMID] 32510613.
2020
Functional Pathway Identification With CRISPR/Cas9 Genome-wide Gene Disruption in Human Dopaminergic Neuronal Cells Following Chronic Treatment With Dieldrin.
Toxicological sciences : an official journal of the Society of Toxicology. 176(2):366-381 [DOI] 10.1093/toxsci/kfaa071.
2020
An electrochemical method to rapidly assess the environmental risk of silver release from nanowire transparent conductive films
NanoImpact (Amsterdam). 18 [DOI] 10.1016/j.impact.2020.100217.
2020
CXL146, a Novel 4H-Chromene Derivative, Targets GRP78 to Selectively Eliminate Multidrug-Resistant Cancer Cells.
Molecular pharmacology. 97(6):402-408 [DOI] 10.1124/mol.119.118745. [PMID] 32276963.
2020
Functional Dependency Analysis Identifies Potential Druggable Targets in Acute Myeloid Leukemia.
Cancers. 12(12) [DOI] 10.3390/cancers12123710. [PMID] 33321907.
2019
Biallelic HEPHL1 variants impair ferroxidase activity and cause an abnormal hair phenotype.
PLoS genetics. 15(5) [DOI] 10.1371/journal.pgen.1008143. [PMID] 31125343.
2019
Crumpling of silver nanowires by endolysosomes strongly reduces toxicity.
Proceedings of the National Academy of Sciences of the United States of America. 116(30):14893-14898 [DOI] 10.1073/pnas.1820041116. [PMID] 31285331.
2019
Functional Profiling Identifies Determinants of Arsenic Trioxide Cellular Toxicity.
Toxicological sciences : an official journal of the Society of Toxicology. 169(1):108-121 [DOI] 10.1093/toxsci/kfz024. [PMID] 30815697.
2019
Genome-Wide CRISPR Screening Identifies the Tumor Suppressor Candidate OVCA2 As a Determinant of Tolerance to Acetaldehyde.
Toxicological sciences : an official journal of the Society of Toxicology. 169(1):235-245 [DOI] 10.1093/toxsci/kfz037. [PMID] 31059574.
2019
HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries.
Journal of visualized experiments : JoVE. (145) [DOI] 10.3791/59382. [PMID] 30985763.
2019
Multi-copper ferroxidase deficiency leads to iron accumulation and oxidative damage in astrocytes and oligodendrocytes.
Scientific reports. 9(1) [DOI] 10.1038/s41598-019-46019-9. [PMID] 31263155.
2019
Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition.
Cell host & microbe. 26(2):252-264.e10 [DOI] 10.1016/j.chom.2019.07.004. [PMID] 31399369.
2019
Propagation of functional estrogen receptor positive normal human breast cells in 3D cultures.
Breast cancer research and treatment. 176(1):131-140 [DOI] 10.1007/s10549-019-05229-5. [PMID] 30993572.
2018
Transcriptomic and Network Analyses Reveal Mechanistic-Based Biomarkers of Endocrine Disruption in the Marine Mussel, Mytilus edulis.
Environmental science & technology. 52(16):9419-9430 [DOI] 10.1021/acs.est.8b01604. [PMID] 29953215.
2018
The Toxicogenome of Hyalella Azteca: a Model for Sediment Ecotoxicology and Evolutionary Toxicology
Environmental science & technology. 52(10):6009-6022 [DOI] 10.1021/acs.est.8b00837. [PMID] 29634279.
2018
Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin
Cellular And Molecular Gastroenterology And Hepatology. 6(4):405-427 [DOI] 10.1016/j.jcmgh.2018.06.006.
2018
Multi-Copper Ferroxidase-Deficient Mice Have Increased Brain Iron Concentrations and Learning and Memory Deficits.
The Journal of nutrition. 148(4):643-649 [DOI] 10.1093/jn/nxy012. [PMID] 29659961.
2018
CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia.
Blood. 132(8):837-848 [DOI] 10.1182/blood-2017-11-814319. [PMID] 29760161.
2018
Multiple environmental stressors induce complex transcriptomic responses indicative of phenotypic outcomes in Western fence lizard.
BMC genomics. 19(1) [DOI] 10.1186/s12864-018-5270-0. [PMID] 30518325.
2018
Ceruloplasmin and hephaestin jointly protect the exocrine pancreas against oxidative damage by facilitating iron efflux.
Redox biology. 17:432-439 [DOI] 10.1016/j.redox.2018.05.013. [PMID] 29883959.
2017
Design and Testing of Safer, More Effective Preservatives for Consumer Products
ACS Sustainable Chemistry & Engineering. 5(5, SI):4320-4331 [DOI] 10.1021/acssuschemeng.7b00374.
2017
Hamp1 Mrna and Plasma Hepcidin Levels Are Influenced By Sex and Strain But Do Not Predict Tissue Iron Levels in Inbred Mice
American Journal of Physiology-Gastrointestinal and Liver Physiology. 313(5):G511-G523 [DOI] 10.1152/ajpgi.00307.2016. [PMID] 28798083.
2017
Intestinal hephaestin potentiates iron absorption in weanling, adult, and pregnant mice under physiological conditions.
Blood advances. 1(17):1335-1346 [DOI] 10.1182/bloodadvances.2017008359. [PMID] 29296776.
2017
Nicotinamide N-methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes.
Hepatology communications. 1(8):803-815 [DOI] 10.1002/hep4.1083. [PMID] 29404495.
2016
Hephaestin and Ceruloplasmin Facilitate Iron Metabolism in the Mouse Kidney
Scientific Reports. 6(1) [DOI] 10.1038/srep39470. [PMID] 27991585.
2015
Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis.
Genes & nutrition. 10(1) [DOI] 10.1007/s12263-014-0443-1. [PMID] 25427953.
2015
Iron deficiency upregulates Egr1 expression.
Genes & nutrition. 10(4) [DOI] 10.1007/s12263-015-0468-0. [PMID] 25981695.
2014
Molecular Signature and Dna Damage Pathways Altered in Male Largemouth Bass (Micropterus Salmoides) By a Single Dose of Benzene and Trichloroethylene
Environmental and Molecular Mutagenesis. 55(1)
2014
Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides).
Aquatic toxicology (Amsterdam, Netherlands). 152:186-94 [DOI] 10.1016/j.aquatox.2014.04.004. [PMID] 24794047.
2013
A Genome-Wide Screen Identifies Yeast Genes Required for Tolerance To Technical Toxaphene, An Organochlorinated Pesticide Mixture
PLoS One. 8(11) [DOI] 10.1371/journal.pone.0081253. [PMID] 24260565.
2013
Cytosolic Ferroxidase (Cytofox) Activity in Rodent Enterocytes Is Independent of Ceruloplasmin and Amyloid Precursor Protein
American Journal of Hematology. 88:E193-E194
2013
Functional Profiling Discovers the Dieldrin Organochlorinated Pesticide Affects Leucine Availability in Yeast
Toxicological Sciences. 132(2):347-358 [DOI] 10.1093/toxsci/kft018. [PMID] 23358190.
2013
Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: the NIEHS Nano GO Consortium.
Environmental health perspectives. 121(6):683-90 [DOI] 10.1289/ehp.1306561. [PMID] 23649538.
2012
Intestinal iron absorption.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 26(2-3):115-9 [DOI] 10.1016/j.jtemb.2012.03.015. [PMID] 22575541.
2011
Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity.
Environmental health perspectives. 119(6):771-7 [DOI] 10.1289/ehp.1002733. [PMID] 21193388.
2011
Linking molecular biomarkers with higher level condition indicators to identify effects of copper exposures on the endangered delta smelt (Hypomesus transpacificus).
Environmental toxicology and chemistry. 30(2):290-300 [DOI] 10.1002/etc.400. [PMID] 21072851.
2010
Quantification of water solubilized CdSe/ZnS quantum dots in Daphnia magna.
Environmental science & technology. 44(5):1841-6 [DOI] 10.1021/es902728a. [PMID] 20131897.
2010
Systems biology of human benzene exposure.
Chemico-biological interactions. 184(1-2):86-93 [DOI] 10.1016/j.cbi.2009.12.011. [PMID] 20026094.
2009
Linking mechanistic and behavioral responses to sublethal esfenvalerate exposure in the endangered delta smelt; Hypomesus transpacificus (Fam. Osmeridae).
BMC genomics. 10 [DOI] 10.1186/1471-2164-10-608. [PMID] 20003521.
2009
Mammalian iron transport.
Cellular and molecular life sciences : CMLS. 66(20):3241-61 [DOI] 10.1007/s00018-009-0051-1. [PMID] 19484405.
2009
Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure.
Toxicology and applied pharmacology. 241(3):294-302 [DOI] 10.1016/j.taap.2009.08.027. [PMID] 19732783.
2009
Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity.
Carcinogenesis. 30(1):50-8 [DOI] 10.1093/carcin/bgn249. [PMID] 18978339.
2008
Déjà vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins.
Proteomics. 8(9):1744-9 [DOI] 10.1002/pmic.200700919. [PMID] 18442176.
2007
Iron-independent specific protein expression pattern in the liver of HFE-deficient mice.
The international journal of biochemistry & cell biology. 39(5):1006-15 [PMID] 17376729.
View on: PubMed
2007
Proteomic analysis of hepatic iron overload in mice suggests dysregulation of urea cycle, impairment of fatty acid oxidation, and changes in the methylation cycle.
American journal of physiology. Gastrointestinal and liver physiology. 292(6):G1490-8 [PMID] 17307722.
View on: PubMed
2006
Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines.
Biological research. 39(1):125-42 [PMID] 16629173.
View on: PubMed
2005
Identification of an intestinal heme transporter.
Cell. 122(5):789-801 [PMID] 16143108.
View on: PubMed
2005
Mechanisms of haem and non-haem iron absorption: lessons from inherited disorders of iron metabolism.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 18(4):339-48 [PMID] 16158226.
View on: PubMed
2005
The role of duodenal cytochrome b in intestinal iron absorption remains unclear.
Blood. 106(13) [PMID] 16326980.
View on: PubMed
2004
Gene expression profiling in chronic copper overload reveals upregulation of Prnp and App.
Physiological genomics. 20(1):45-54 [PMID] 15467011.
View on: PubMed
2004
Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE.
British journal of haematology. 126(3):434-6 [PMID] 15257718.
View on: PubMed
2002
Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats.
Gastroenterology. 123(3):835-44 [PMID] 12198710.
View on: PubMed
2002
The ceruloplasmin homolog hephaestin and the control of intestinal iron absorption.
Blood cells, molecules & diseases. 29(3):367-75 [PMID] 12547227.
View on: PubMed
2002
The expression and regulation of the iron transport molecules hephaestin and IREG1: implications for the control of iron export from the small intestine.
Cell biochemistry and biophysics. 36(2-3):137-46 [PMID] 12139399.
View on: PubMed

Grants

Feb 2021 ACTIVE
Fibroblast cell isolation and expansion and iPSC derivation in purebred Maine Coon and Ragdoll cats
Role: Other
Funding: AM COLL OF VET INTERNAL MED via NESTLE PURINA PETCARE COMPANY
Jan 2021 ACTIVE
D21CA-042: A CRISPR/Cas9 homology-independent targeted insertion (HITI) strategy to advance gene therapy in canine iPSC-derived cardiomyocytes
Role: Co-Investigator
Funding: MORRIS ANIMAL FOU
Sep 2020 ACTIVE
Development of HITI CRISPR gene therapy for dilated cardiomyopathy in a canine model
Role: Principal Investigator
Funding: SAREPTA THERAPEUTICS
Jul 2020 ACTIVE
OR-DRPD-ROF2020: A humanized peroxisome proliferator activated receptor alpha (PPARa) zebrafish: A new transgenic model for obesogenic chemical screening
Role: Co-Investigator
Funding: UF RESEARCH
Jul 2019 – Aug 2020
Role of Bcl11b in CD4+ T cells and innate lymphoid cells
Role: Project Manager
Funding: NATL INST OF HLTH NIAID
Jul 2019 ACTIVE
Together: Transforming and Translating Discovery to Improve Health
Role: Project Manager
Funding: NATL INST OF HLTH NCATS
Jun 2018 ACTIVE
OR-DRPD-ROD2018: Development of Leukemia-Oncotype Prototype CARS (Cytarabine AML Response Score) for Prediction of Relapse Risk in AML
Role: Co-Investigator
Funding: UF RESEARCH
Sep 2017 ACTIVE
UFHCC Triple Negative Breast Cancer (TNBC) Pilot Project Program
Role: Project Manager
Funding: MULTIPLE SPONSORS
Jun 2017 – Apr 2018
CRISPR-CAS9 Genomic Screening COR
Role: Principal Investigator
Funding: US ENVIRONMENTAL PRO AGCY
Apr 2017 ACTIVE
OoR CTSI Institutional Matching Support
Role: Project Manager
Funding: UF DIV OF SPONSORED RES MATCHING FUNDS
Mar 2017 – Mar 2018
Improved in vitro metabolism in HepG2 cells using CRISPRa Technology
Role: Principal Investigator
Funding: JOHNS HOPKINS UNIV
Sep 2016 ACTIVE
Southeastern and Coastal Center for Agricultural Health and Safety (SCC-AHS)
Role: Project Manager
Funding: CTRS FOR DIS CNTRL INST OCCUP SFTY HLTH
Sep 2016 – Dec 2020
Nanowire Intelligent Re-design and Recycling for Environmental Safety
Role: Principal Investigator
Funding: CONSUMER PRODUCT SAFETY COMM
Aug 2016 – Feb 2020
Environmental and Genetic Determinants of Transitional Cell Carcinoma of the Urinary Tract in Scottish Terriers funded by Olive's Way
Role: Co-Investigator
Funding: UF FOU
Jul 2016 – Jul 2017
Transform Tox Testing Challenge: Innovating for Metabolism
Role: Principal Investigator
Funding: US ENVIRONMENTAL PRO AGCY
Jun 2016 – May 2018
Functional screening to identify mediators of dopaminergic neuronal toxicity by pesticides
Role: Principal Investigator
Funding: UF DSR OPPORTUNITY FUND
Nov 2015 – Dec 2016
Genomic Differences in response of daphnia magna
Role: Principal Investigator
Funding: INTL COPPER ASSOC
Sep 2015 – Jun 2018
High throughput transcriptional profiling of human mammary stem cell denived organoids
Role: Principal Investigator
Funding: LAWRENCE BERKELEY NATL LAB via US DEPT OF ENERGY
Jun 2015 – May 2018
An Integrated molecular approach to understand
Role: Principal Investigator
Funding: NATL INST OF HLTH NIGMS
May 2015 – Apr 2019
Functional Profiling to Identify Mitochondria-cell Signaling Networks
Role: Principal Investigator
Funding: NATL INST OF HLTH NIEHS
Jan 2015 – May 2020
Investigating Biogeochenical Controls on Metal Toxicity Using Stable Isotopes
Role: Principal Investigator
Funding: COLORADO SCHOOL OF MINES via NATL INST OF HLTH NIEHS

Education

M.D., Medicine
1996 · University of California
Ph.D., Biochemistry, Genetics
1994 · University of California
S.B., Biology
1986 · Massachusetts Institute of Technology

Teaching Profile

Courses Taught
2019-2021
PHC7979 Advanced Research
2018-2021
VEM5131 Vet Molecular Biology
2020
HUN6936 Topics in Nutritional Sciences
2017-2019
VEM5171 Vet Pharmacology
2019
VEM5172 Veterinary Toxicology
2018
VME7980 Research for Doctoral Dissertation
2018
PHC6937 Special Topics in Public Health
2016
VME6905 Problems in Veterinary Medical Sciences
2015
VME6932 Seminar in Physiological Sciences
2021
PHC7980 Research for Doctoral Dissertation
2021
GMS6012 Human Genetics

Contact Details

Phones:
Business:
(650) 291-5679
Emails:
Business:
cvulpe@ufl.edu

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