Jennifer Freedman

Positions:

Assistant Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2001

Emory University

Grants:

Publications:

Genetic requirements for spontaneous and transcription-stimulated mitotic recombination in Saccharomyces cerevisiae.

The genetic requirements for spontaneous and transcription-stimulated mitotic recombination were determined using a recombination system that employs heterochromosomal lys2 substrates that can recombine only by crossover or only by gene conversion. The substrates were fused either to a constitutive low-level promoter (pLYS) or to a highly inducible promoter (pGAL). In the case of the "conversion-only" substrates the use of heterologous promoters allowed either the donor or the recipient allele to be highly transcribed. Transcription of the donor allele stimulated gene conversions in rad50, rad51, rad54, and rad59 mutants, but not in rad52, rad55, and rad57 mutants. In contrast, transcription of the recipient allele stimulated gene conversions in rad50, rad51, rad54, rad55, rad57, and rad59 mutants, but not in rad52 mutants. Finally, transcription stimulated crossovers in rad50, rad54, and rad59 mutants, but not in rad51, rad52, rad55, and rad57 mutants. These data are considered in relation to previously proposed molecular mechanisms of transcription-stimulated recombination and in relation to the roles of the recombination proteins.
MLA Citation
Freedman, Jennifer A., and Sue Jinks-Robertson. “Genetic requirements for spontaneous and transcription-stimulated mitotic recombination in Saccharomyces cerevisiae.Genetics, vol. 162, no. 1, Sept. 2002, pp. 15–27.
URI
https://scholars.duke.edu/individual/pub796018
PMID
12242220
Source
pubmed
Published In
Genetics
Volume
162
Published Date
Start Page
15
End Page
27

Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities.

Studies of alternative RNA splicing (ARS) have the potential to provide an abundance of novel targets for development of new biomarkers and therapeutics in oncology, which will be necessary to improve outcomes for patients with cancer and mitigate cancer disparities. ARS, a key step in gene expression enabling individual genes to encode multiple proteins, is emerging as a major driver of abnormal phenotypic heterogeneity. Recent studies have begun to identify RNA splicing-related genetic and genomic variation in tumors, oncogenes dysregulated by ARS, RNA splice variants driving race-related cancer aggressiveness and drug response, spliceosome-dependent transformation, and RNA splicing-related immunogenic epitopes in cancer. In addition, recent studies have begun to identify and test, preclinically and clinically, approaches to modulate and exploit ARS for therapeutic application, including splice-switching oligonucleotides, small molecules targeting RNA splicing or RNA splice variants, and combination regimens with immunotherapies. Although ARS data hold such promise for precision oncology, inclusion of studies of ARS in translational and clinical cancer research remains limited. Technologic developments in sequencing and bioinformatics are being routinely incorporated into clinical oncology that permit investigation of clinically relevant ARS events, yet ARS remains largely overlooked either because of a lack of awareness within the clinical oncology community or perceived barriers to the technical complexity of analyzing ARS. This perspective aims to increase such awareness, propose immediate opportunities to improve identification and analysis of ARS, and call for bioinformaticians and cancer researchers to work together to address the urgent need to incorporate ARS into cancer biology and precision oncology.
Authors
Robinson, TJ; Freedman, JA; Al Abo, M; Deveaux, AE; LaCroix, B; Patierno, BM; George, DJ; Patierno, SR
MLA Citation
Robinson, Timothy J., et al. “Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities.Clin Cancer Res, vol. 25, no. 10, May 2019, pp. 2963–68. Pubmed, doi:10.1158/1078-0432.CCR-18-2445.
URI
https://scholars.duke.edu/individual/pub1370310
PMID
30755441
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
25
Published Date
Start Page
2963
End Page
2968
DOI
10.1158/1078-0432.CCR-18-2445

Polychaetoid is required to restrict segregation of sensory organ precursors from proneural clusters in Drosophila.

Reduction of wild-type activity of the polychaetoid (pyd) gene results in formation of extra mechanosensory bristles on the head and notum of adult Drosophila. Loss of pyd function results in decreased ability to restrict sensory organ precursor (SOP) formation to a single cell per proneural cluster. Although the initial proneural cluster pattern of achaete expression is not altered in pyd mutants, extra cells within proneural clusters express the high levels of achaete characteristic of SOPs. This observation suggests that pyd+ functions as a negative regulator of achaete-scute complex expression within the proneural cluster. Synergistic interactions between pyd and Notch, Delta and extramacrochaetae mutations support this model. We also demonstrate that pyd is required for normal eye development.
Authors
Chen, CM; Freedman, JA; Bettler, DR; Manning, SD; Giep, SN; Steiner, J; Ellis, HM
MLA Citation
Chen, C. M., et al. “Polychaetoid is required to restrict segregation of sensory organ precursors from proneural clusters in Drosophila.Mech Dev, vol. 57, no. 2, July 1996, pp. 215–27. Pubmed, doi:10.1016/0925-4773(96)00548-5.
URI
https://scholars.duke.edu/individual/pub963897
PMID
8843398
Source
pubmed
Published In
Mechanisms of Development
Volume
57
Published Date
Start Page
215
End Page
227
DOI
10.1016/0925-4773(96)00548-5

Single-nucleotide polymorphisms of stemness genes predicted to regulate RNA splicing, microRNA and oncogenic signaling are associated with prostate cancer survival.

Prostate cancer (PCa) is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single-nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with PCa survival. SNPs within stemness-related genes were analyzed for association with overall survival of PCa in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Significant SNPs predicted to be functional were selected for linkage disequilibrium analysis and combined and stratified analyses. Identified SNPs were evaluated for association with gene expression. SNPs of CD44 (rs9666607), ABCC1 (rs35605 and rs212091) and GDF15 (rs1058587) were associated with PCa survival and predicted to be functional. A role for rs9666607 of CD44 and rs35605 of ABCC1 in RNA splicing regulation, rs212091 of ABCC1 in miRNA binding site activity and rs1058587 of GDF15 in causing an amino acid change was predicted. These SNPs represent potential novel prognostic markers for overall survival of PCa and support a contribution of the stemness pathway to PCa patient outcome.
Authors
Freedman, JA; Wang, Y; Li, X; Liu, H; Moorman, PG; George, DJ; Lee, NH; Hyslop, T; Wei, Q; Patierno, SR
MLA Citation
Freedman, Jennifer A., et al. “Single-nucleotide polymorphisms of stemness genes predicted to regulate RNA splicing, microRNA and oncogenic signaling are associated with prostate cancer survival.Carcinogenesis, vol. 39, no. 7, July 2018, pp. 879–88. Pubmed, doi:10.1093/carcin/bgy062.
URI
https://scholars.duke.edu/individual/pub1315762
PMID
29726910
Source
pubmed
Published In
Carcinogenesis
Volume
39
Published Date
Start Page
879
End Page
888
DOI
10.1093/carcin/bgy062

Corrigendum: Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer.

This corrects the article DOI: 10.1038/ncomms15921.
Authors
Wang, B-D; Ceniccola, K; Hwang, S; Andrawis, R; Horvath, A; Freedman, JA; Olender, J; Knapp, S; Ching, T; Garmire, L; Patel, V; Garcia-Blanco, MA; Patierno, SR; Lee, NH
MLA Citation
Wang, Bi-Dar, et al. “Corrigendum: Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer.Nat Commun, vol. 8, Sept. 2017, p. 16161. Pubmed, doi:10.1038/ncomms16161.
URI
https://scholars.duke.edu/individual/pub1277855
PMID
28952599
Source
pubmed
Published In
Nature Communications
Volume
8
Published Date
Start Page
16161
DOI
10.1038/ncomms16161