Jason Somarelli

Positions:

Assistant Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Assistant Professor

Marine Science and Conservation
Nicholas School of the Environment

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2009

Florida International University

Grants:

Targeting the p38/Snail/PD-L1 axis in hormone-therapy resistance and metastasis

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Targeting Convergent Mechanisms of Therapy Resistance, Metastasis, and Immune Evasion with CBP inhibitors

Administered By
Medicine, Medical Oncology
Awarded By
FORMA Therapeutics, Inc.
Role
Principal Investigator
Start Date
End Date

Testing the efficacy of AR degrading compounds in enzalutamide-resistant prostate cancer

Administered By
Medicine, Medical Oncology
Awarded By
Arvinas Inc.
Role
Principal Investigator
Start Date
End Date

Marine Mammals Point the Way Toward New Therapies to Prevent Hypoxia

Administered By
Medicine, Medical Oncology
Awarded By
Dolphin Quest
Role
Principal Investigator
Start Date
End Date

Scholars in Marine Medicine: Mentored Research at the Nexus of the Marine Environment and Human Health.

Administered By
Medicine, Medical Oncology
Awarded By
Dolphin Quest
Role
Principal Investigator
Start Date
End Date

Publications:

ASO Author Reflections: Identifying Modifiable and Non-Modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma.

Authors
MLA Citation
Lazarides, Alexander L., et al. “ASO Author Reflections: Identifying Modifiable and Non-Modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma.Ann Surg Oncol, Oct. 2021. Pubmed, doi:10.1245/s10434-021-10904-3.
URI
https://scholars.duke.edu/individual/pub1499473
PMID
34635971
Source
pubmed
Published In
Annals of Surgical Oncology
Published Date
DOI
10.1245/s10434-021-10904-3

The somatic molecular evolution of cancer: Mutation, selection, and epistasis

Cancer progression has been attributed to somatic changes in single-nucleotide variants, copy-number aberrations, loss of heterozygosity, chromosomal instability, epistatic interactions, and the tumor microenvironment. It is not entirely clear which of these changes are essential and which are ancillary to cancer. The dynamic nature of cancer evolution in a patient can be illuminated using several concepts and tools from classical evolutionary biology. Neutral mutation rates in cancer cells are calculable from genomic data such as synonymous mutations, and selective pressures are calculable from rates of fixation occurring beyond the expectation by neutral mutation and drift. However, these cancer effect sizes of mutations are complicated by epistatic interactions that can determine the likely sequence of gene mutations. In turn, longitudinal phylogenetic analyses of somatic cancer progression offer an opportunity to identify key moments in cancer evolution, relating the timing of driver mutations to corresponding landmarks in the clinical timeline. These analyses reveal temporal aspects of genetic and phenotypic change during tumorigenesis and across clinical timescales. Using a related framework, clonal deconvolution, physical locations of clones, and their phylogenetic relations can be used to infer tumor migration histories. Additionally, genetic interactions with the tumor microenvironment can be analyzed with longstanding approaches applied to organismal genotype-by-environment interactions. Fitness landscapes for cancer evolution relating to genotype, phenotype, and environment could enable more accurate, personalized therapeutic strategies. An understanding of the trajectories underlying the evolution of neoplasms, primary, and metastatic tumors promises fundamental advances toward accurate and personalized predictions of therapeutic response.
Authors
Dasari, K; Somarelli, JA; Kumar, S; Townsend, JP
MLA Citation
Dasari, K., et al. “The somatic molecular evolution of cancer: Mutation, selection, and epistasis.” Progress in Biophysics and Molecular Biology, vol. 165, Oct. 2021, pp. 56–65. Scopus, doi:10.1016/j.pbiomolbio.2021.08.003.
URI
https://scholars.duke.edu/individual/pub1494455
Source
scopus
Published In
Progress in Biophysics and Molecular Biology
Volume
165
Published Date
Start Page
56
End Page
65
DOI
10.1016/j.pbiomolbio.2021.08.003

Klf4 induces mesenchymal–epithelial transition (Met) by suppressing multiple emt‐inducing transcription factors

Epithelial–Mesenchymal Plasticity (EMP) refers to reversible dynamic processes where cells can transition from epithelial to mesenchymal (EMT) or from mesenchymal to epithelial (MET) phenotypes. Both these processes are modulated by multiple transcription factors acting in concert. While EMT‐inducing transcription factors (TFs)—TWIST1/2, ZEB1/2, SNAIL1/2/3, GSC, and FOXC2—are well‐characterized, the MET‐inducing TFs are relatively poorly understood (OVOL1/2 and GRHL1/2). Here, using mechanism‐based mathematical modeling, we show that transcription factor KLF4 can delay the onset of EMT by suppressing multiple EMT‐TFs. Our simulations suggest that KLF4 overexpression can promote a phenotypic shift toward a more epithelial state, an obser-vation suggested by the negative correlation of KLF4 with EMT‐TFs and with transcriptomic‐based EMT scoring metrics in cancer cell lines. We also show that the influence of KLF4 in modulating the EMT dynamics can be strengthened by its ability to inhibit cell‐state transitions at the epigenetic level. Thus, KLF4 can inhibit EMT through multiple parallel paths and can act as a putative MET‐ TF. KLF4 associates with the patient survival metrics across multiple cancers in a context‐specific manner, highlighting the complex association of EMP with patient survival.
Authors
Subbalakshmi, AR; Sahoo, S; McMullen, I; Saxena, AN; Venugopal, SK; Somarelli, JA; Jolly, MK
MLA Citation
Subbalakshmi, A. R., et al. “Klf4 induces mesenchymal–epithelial transition (Met) by suppressing multiple emt‐inducing transcription factors.” Cancers, vol. 13, no. 20, Oct. 2021. Scopus, doi:10.3390/cancers13205135.
URI
https://scholars.duke.edu/individual/pub1499524
Source
scopus
Published In
Cancers
Volume
13
Published Date
DOI
10.3390/cancers13205135

Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma: A National Cancer Database Study.

BACKGROUND: Limited data are available to inform the risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following surgical resection of chondrosarcoma. METHODS: We retrospectively reviewed 6653 patients following surgical resection of primary chondrosarcoma in the National Cancer Database (2004-2017). Both demographic and clinicopathologic variables were assessed for correlation with readmission and short-term mortality utilizing univariate and multivariate logistic regression modeling. RESULTS: Of 220 readmissions (3.26%), risk factors independently associated with an increased risk of unplanned 30-day readmission included Charlson-Deyo Comorbidity Index (CDCC) (odds ratio [OR] 1.31; p = 0.027), increasing American Joint Committee on Cancer (AJCC) stage (OR 1.31; p = 0.004), undergoing major amputation (OR 2.38; p = 0.001), and axial skeletal location (OR 1.51; p = 0.028). A total of 137 patients died within 90 days of surgery (2.25%). Risk factors associated with increased mortality included the CDCC (OR 1.60; p = 0.001), increasing age (OR 1.06; p < 0.001), having Medicaid insurance status (OR 3.453; p = 0.005), living in a zip code with a higher educational attainment (OR 1.59; p = 0.003), increasing AJCC stage (OR 2.32; p < 0.001), longer postoperative length of stay (OR 1.015; p = 0.033), and positive surgical margins (OR 2.75; p = 0.001). Although a majority of the cohort did not receive radiation therapy (88.8%), receiving radiotherapy (OR 0.132; p = 0.010) was associated with a decreased risk of short-term mortality. CONCLUSIONS: Several tumor, treatment, and patient factors can help inform the risk of readmission and short-term mortality in patients with surgically treated chondrosarcoma.
Authors
Evans, DR; Lazarides, AL; Cullen, MM; Somarelli, JA; Blazer, DG; Visguass, JD; Brigman, BE; Eward, WC
MLA Citation
Evans, Daniel R., et al. “Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma: A National Cancer Database Study.Ann Surg Oncol, Sept. 2021. Pubmed, doi:10.1245/s10434-021-10802-8.
URI
https://scholars.duke.edu/individual/pub1497734
PMID
34570333
Source
pubmed
Published In
Annals of Surgical Oncology
Published Date
DOI
10.1245/s10434-021-10802-8

The Hallmarks of Cancer as Ecologically Driven Phenotypes

Ecological fitness is the ability of individuals in a population to survive and reproduce. Individuals with increased fitness are better equipped to withstand the selective pressures of their environments. This paradigm pertains to all organismal life as we know it; however, it is also becoming increasingly clear that within multicellular organisms exist highly complex, competitive, and cooperative populations of cells under many of the same ecological and evolutionary constraints as populations of individuals in nature. In this review I discuss the parallels between populations of cancer cells and populations of individuals in the wild, highlighting how individuals in either context are constrained by their environments to converge on a small number of critical phenotypes to ensure survival and future reproductive success. I argue that the hallmarks of cancer can be distilled into key phenotypes necessary for cancer cell fitness: survival and reproduction. I posit that for therapeutic strategies to be maximally beneficial, they should seek to subvert these ecologically driven phenotypic responses.
Authors
MLA Citation
Somarelli, J. A. “The Hallmarks of Cancer as Ecologically Driven Phenotypes.” Frontiers in Ecology and Evolution, vol. 9, Apr. 2021. Scopus, doi:10.3389/fevo.2021.661583.
URI
https://scholars.duke.edu/individual/pub1483635
Source
scopus
Published In
Frontiers in Ecology and Evolution
Volume
9
Published Date
DOI
10.3389/fevo.2021.661583