Download OMB No. 0925-0046, Biographical Sketch Format Page

OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
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NAME: Jackie A. Fretz, Ph.D.
POSITION TITLE: Assistant Professor
eRA COMMONS USER NAME (credential, e.g., agency login): JFRETZ
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency
training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
Completion Date
MM/YYYY
FIELD OF STUDY
University of New Hampshire; Durham, NH
B.S.
2002
Biochemistry
University of Wisconsin-Madison; Madison, WI
Ph.D.
2007
Biochemistry
Yale University; New Haven, CT
Postdoctoral 2011
Molecular Biology
A. Personal Statement
My research focuses on investigation of the roles of the transcription factor Early B cell factor 1 (Ebf1) and
the mechanisms of transcriptional regulation by this protein in kidney function and development. I have a
broad background in biochemistry and molecular biology techniques, and specifically with transcription
factors involved in differentiation of mesenchymal lineage cells. I am proficient in many techniques relevant
to this field of study from in vitro binding assays, and transcriptional reporter studies to in vivo examination
of metabolic and homeostatic phenotypes present in animal models. As a PI on several university- and NIHfunded grants, I have experience successfully managing project execution (e.g. staffing, research, budget),
collaborating with other researchers, and producing peer-reviewed publications from these projects in high
impact journals including Cell and Cell Metabolism. I have been focused on understanding the functions of
Ebf1 in kidney for the past 5 years. Although my research has not been restricted to a single tissue type or
particular mesenchymal lineage over my career it has been my keen observational skill and awareness of
cross-tissue intricacies that has propelled this work forward, produced novel insights into the nuanced
differences in mesenchymal stem cells, and led to the discovery of completely new mechanisms of action for
this protein in previously overlooked organs. The current application builds logically on this prior work.
B. Positions and Honors
Positions and Employment
1999-2002
Laboratory Assistant, UNH Research Greenhouses, UNH, Durham, NH, CT
2000-2002
Undergraduate Researcher, Nutritional Sciences Department, UNH, Durham, NH, CT
2002-2007
Graduate Student, Biochemistry Department, UW-Madison, Madison, WI, CT
2007-2007
Postdoctoral Researcher, Biochemistry Department, UW-Madison, Madison, WI, CT
2008-2011
Postdoctoral Associate, Orthopaedics Department, Yale School of Medicine, New Haven, CT
2011-2014
Associate Research Scientist, Orthopaedics Department, Yale School of Medicine, New Haven,
CT
2014Assistant Professor, Orthopaedics Department, Yale School of Medicine, New Haven, CT
Other Experience and Professional Memberships
2004-2006
2005-2006
Coordinator, Biochemistry Peer Mentor Tutoring Program, UW-Madison, Madison, WI
Chair, Biochemistry Student Faculty Liaison Committee, UW-Madison, Madison, WI
20052011-
Member, American Society for Bone and Mineral Research (ASBMR)
Member, American Society of Nephrology (ASN)
Honors
2001
2001
2002
2006
2009
2009
2009
2010
2011
2015
UNH Summer Undergraduate Research Fellowship
American Heart Association of New England Undergraduate Research Fellowship
Movers and Shakers Award, UNH, Durham, NH
Graduate Excellence in Teaching Award, Biochemistry, UW-Madison, Madison, WI
ASBMR Young Investigator Award, Frontiers in Skeletal Research: Bone, Fat and Brain
Connections, Bethesda, MD
Plenary Poster, New Frontiers in Skeletal Research: Bone, Fat and Brain Connections,
Bethesda, MD
Plenary Poster, ASBMR 31st Annual Meeting, Denver, CO
John Haddad Young Investigator Award, Advances in Mineral Metabolism and American
Society for Bone and Mineral Research
ASBMR President’s Poster Award, Annual Meeting San Diego, CA
Plenary Poster, ASBMR 35th Annual Meeting, Seattle, WA
C. Contribution to Science
1. My early work focused on transcriptional regulation within bone building osteoblasts and bone resorbing
osteoclasts. Our laboratory was a frontier research group for the implementation of chromatin
immunoprecipitation (ChIP) to investigate genome-wide binding of transcription factors within their native
chromatin environments. Specifically we focused on identifying novel regulatory elements and target genes
for the vitamin D receptor (VDR) within osteoblasts, and transcriptional regulation by nuclear factor of
activated T cells 1 (Nfatc1) in osteoclasts. In osteoblasts we identified many unique VDR target genes,
including Lrp5, and discovered the long sought after distal VDR enhancer regions of Rankl (Tnfsf11), which
contain vitamin D response elements 76 Kb upstream from that gene’s transcriptional start site. Within
osteoclasts we were able to demonstrate autoregulation of Nfatc1 within the developing osteoclast, and also
identified numerous Nfatc1 binding sites within key osteoclast-associated genes including tartrate resistant
acid phosphatase.
a. Fretz JA, Zella LA, Kim S, Shevde NK, Pike JW. (2006). 1,25-Dihydroxyvitamin D3 regulates the
expression of low-density lipoprotein receptor-related protein 5 via deoxyribonucleic acid sequence
elements located downstream of the start site of transcription. Mol Endocrinol 20(9):2215-30. PMC
Journal– In Process
b. Kim S, Yamazaki M, Zella LA, Meyer MB, Fretz JA, Shevde NK, Pike JW. (2007). Multiple
enhancer regions located at significant distances upstream of the transcriptional start site mediate
RANKL gene expression in response to 1,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol
103(3-5):430-4. PMCID: PMC1892901
c. Fretz JA, Zella LA, Kim S, Shevde NK, Pike JW. (2007). 1,25-Dihydroxyvitamin D3 induces
expression of the Wnt signaling co-regulator LRP5 via regulatory elements located significantly
downstream of the gene's transcriptional start site. J Steroid Biochem Mol Biol 103(3-5):440-5.
PMCID: PMC1868540
d. Pike JW, Meyer MB, Watanuki M, Kim S, Zella LA, Fretz JA, Yamazaki M, Shevde NK. (2007).
Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor. J
Steroid Biochem Mol Biol 103(3-5):389-95. PMCID: PMC1868541
e. Galli C, Zella LA, Fretz JA, Fu Q, Pike JW, Weinstein RS, Manolagas SC, O'Brien CA. (2008).
Targeted deletion of a distant transcriptional enhancer of the receptor activator of nuclear factor{kappa} b ligand gene reduces bone remodeling and increases bone mass. Endocrinology
149(1):146-53. PMCID: PMC2194617
f. Fretz JA, Shevde NK, Singh S, Darnay BG, Pike JW. (2008). RANKL-induced nuclear factor of
activated T cells (c1) autoregulates its own expression in osteoclasts and mediates the upregulation
of tartrate-resistant acid phosphatase. Mol Endocrinol 22(3):737-50. PMCID: PMC2262172
2. My postdoctoral research focused on transcriptional regulation by Early B cell factor 1 (Ebf1). We were
originally interested in the actions of Ebf1 as a way to interrogate the contribution of B cells to the bone
marrow hematopoietic stem cell niche, however we discovered it had wider influence on the bone marrow
environment through direct actions in the mesenchymal lineage. I demonstrated that the mesenchymal
progenitor of marrow adipocytes is distinct from the progenitors in peripheral adipose. Furthermore, while
peripheral adipocytes are highly dependent upon the expression of Ebf1 for development, bone marrow
adipocytes do not share this dependence upon Ebf1 expression. These investigations also brought about
the implementation and refinement of a novel laboratory technique, osmium staining coupled with microCT imaging of marrow adipocytes, to visualize and quantify accumulation of these cells in vivo.
a. Hesslein DG, Fretz JA, Xi Y, Nelson T, Zhou S, Lorenzo JA, Schatz DG, Horowitz MC. (2009).
Ebf1-dependent control of the osteoblast and adipocyte lineages. Bone 44(4):537-46. PMCID: PMC
2657874
b. Fretz JA, Nelson T, Xi Y, Adams DJ, Rosen CJ, Horowitz MC. (2010). Altered Metabolism and
Lipodystrophy in the Ebf1-Deficient Mouse. Endocrinology 151(4):1611-21. PMCID: PMC2657874
c. Horowitz MC, Fretz JA, Lorenzo JA. (2010). How B cells influence bone biology in health and
disease. Bone 47(3):472-9. PMCID: PMC2850234
d. Festa E, Fretz JA, Berry R, Schmidt B, Rodeheffer M, Horowitz MC, Horsley V. (2011). Adipocyte
lineage cells contribute to the skin stem cell niche. Cell 146(5):761-71. PMCID: PMC3298746
e. Scheller EL, Troiano N, Vanhoutan JN, Bouxsein MA, Fretz JA, Xi Y, Nelson T, Katz G, Berry R,
Church CD, Doucette CR, Rodeheffer MS, Macdougald OA, Rosen CJ, Horowitz MC. (2014). Use
of osmium tetroxide staining with microcomputerized tomography to visualize and quantify bone
marrow adipose tissue in vivo. Methods Enzymol. 2014;537:123-39. PMID: 24480344
f. Gao H, Mejhert N, Fretz JA, Arner E, Lorente-Cebrián S, Ehrlund A, Dahlman-Wright K,
Laurencikiene J, Dahlman I, Daub CO, Rydén M, Horowitz MC, Arner P. (2014). Early B-cell Factor
1 Regulates Adipose Morphology and Lipolysis in White Adipose Tissue. Cell Metabolism
19(6):981-92. PMID: 24856929.
g. Berry R, Fretz JA, MacDougald O, Klibanski A, Rosen CJ, Rodeheffer M, Horowitz MC. (2015).
Marrow Adipose Tissue and its Interactions with the Skeletal, Hematopoietic, and Immune Systems.
Osteoimmunology: Interactions of the Immune and Skeletal Systems, 2nd edition. Elsevier 345-352.
ISBN: 978-0-12-800571-2
3. While examining the actions of Ebf1 within adipose and the skeletal system, biomarker abnormalities
lead me to discover that whole body knockout mice had a phenotype that was more widespread than
was previously appreciated, and that these animals exhibited renal insufficiency. I pioneered research
examining the role of Ebf1 within the kidney, which had never before been explored or noticed. Ebf1 is
integral to peripheral cortex development and glomerular function. It is essential for the final stages of
metanephric development via kidney intrinsic mechanisms. My ongoing investigations into the actions of
Ebf1 during cortical and glomerular development are providing novel insights into the pathways
underlying tuft formation and glomerular disease progression.
a. Fretz JA, Nelson T, Velazquez H, Xi Y, Moeckel G, Horowitz MC. (2014). Early B cell factor 1 is an
essential transcription factor for postnatal glomerular maturation. Kidney International 85:1091–
1102. PMID: 24480344
b. Li L, Troiano N, Webb R, Sun B, VanHouten J, Nelson T, Tommasini SM, Fretz JA. (2016). Both
phosphate replacement and high fat diet are necessary to improve survival, bone quality, and
kidney function in Ebf1-deficient mice. JBMR (submitted manuscript).
c. Li L, Troiano N, Webb R, Nelson T, Sun B, Fretz JA. (2016). EBF1 regulates glomerular
development by mediating COX-2 signaling from mesangial cells. JASN (submitted manuscript).
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/jackie.fretz.1/bibliograpahy/43560639/public/?sort=date&direction=as
cending