Publications -- Harlan Jones

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/31773

This collection is limited to articles published under the terms of a creative commons license or other open access publishing agreement since 2016. It is not intended as a complete list of the author's works.

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Short Peptides based on the conserved regions of MIEN1 protein exhibit anti-cancer activity by targeting the MIEN1 Signaling Pathway
(Elsevier B.V., 2024-01-26) Tripathi, Amit K.; Desai, Priyanka P.; Tyagi, Antariksh; Lampe, Jana B.; Srivastava, Yogesh; Donkor, Michael; Jones, Harlan P.; Dzyuba, Sergei V.; Crossley, Eric; Williams, Noelle S.; Vishwanatha, Jamboor K.
Migration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved ITAM and prenylation motifs within MIEN1, we identified potent anti-cancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations. The peptides effectively inhibited genes and proteins driving cancer cell migration, invasion, and EMT pathways, concurrently suppressing EGF-induced NF-kappaB nuclear translocation in metastatic breast cancer cells. Specifically, peptides targeted the same signal transduction pathway initiated by MIEN1. Molecular docking and circular dichroism spectroscopy indicated the formation of MIEN1-peptide complexes. The third-positioned isoleucine in LA3IK and CVIL motif in RP-7 were crucial for inhibiting breast cancer cell migration. This is evident from the limited migration inhibition observed when MDA-MB-231 cells were treated with scrambled peptides LA3IK SCR and RP-7 SCR. Additionally, LA3IK and RP-7 effectively suppressed tumor growth in an orthotopic breast cancer model. Notably, mice tolerated high peptide doses of up to 90 mg/Kg well, surpassing significantly lower doses of 5 mg/Kg intravenously (iv) and 30 mg/Kg intraperitoneally (ip) used in both in vivo pharmacokinetic studies and orthotopic mouse model assays. D-isomers of LA3IK and RP-7 showed enhanced anti-cancer activity compared to their L-isomers. D-LA3IK remained stable in mouse plasma for 24 h with 75% remaining, exhibiting superior pharmacokinetic properties over D/L-RP-7. In summary, our findings mark the first report of short peptides based on MIEN1 protein sequence capable of inhibiting cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo.
Mitochondrial SOS: how mtDNA may act as a stress signal in Alzheimer's disease
(BioMed Central Ltd., 2023-10-12) Gorham, Isabelle K.; Barber, Robert C.; Jones, Harlan P.; Phillips, Nicole R.
BACKGROUND: Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is well known that not only are the mitochondria a key player in producing energy for the cell, but they also are known to interact in other important intracellular processes as well as extracellular signaling and communication. BODY: This mini review explores how cells use mtDNA as a stress signal, particularly in Alzheimer's disease. We investigate the measurement of these mtDNA alterations, the mechanisms of mtDNA release, and the immunological effects from the release of these stress signals. CONCLUSION: Literature indicates a correlation between the release of mtDNA in Alzheimer's disease and increased immune responses, showing promise as a potential biomarker. However, several questions remain unanswered and there is great potential for future studies in this area.
Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses
(MDPI, 2023-02-26) Donkor, Michael; Choe, Jamie Y.; Reid, Danielle; Quinn, Byron; Pulse, Mark; Ranjan, Amalendu P.; Chaudhary, Pankaj; Jones, Harlan P.
Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses. The nasal nano-vaccine-induced T-cell-mediated antitumor mucosal immune response was shown to increase tumor-specific production of IFN-gamma and granzyme B by lung-derived CD8(+) T cells. These findings demonstrate that our engineered nasal nano-vaccine has the potential to be used as a prophylactic approach prior to the seeding of tumors in the lungs, and thereby prevent overt lung metastases from existing extra pulmonary tumors.
Combination of Small Extracellular Vesicle-Derived Annexin A2 Protein and mRNA as a Potential Predictive Biomarker for Chemotherapy Responsiveness in Aggressive Triple-Negative Breast Cancer
(MDPI, 2023-01-09) Desai, Priyanka P.; Narra, Kalyani; James, Johanna D.; Jones, Harlan P.; Tripathi, Amit K.; Vishwanatha, Jamboor K.
Small extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca(2+))-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC). The objective of the current study is to determine whether sEV-AnxA2 protein and/or mRNA could be a useful biomarkers to predict the responsiveness of chemotherapy in TNBC. Removal of Immunoglobulin G (IgG) from the serum as well as using the System Bioscience's ExoQuick Ultra kit resulted in efficient sEV isolation and detection of sEV-AnxA2 protein and mRNA compared to the ultracentrifugation method. The standardized method was applied to the twenty TNBC patient sera for sEV isolation. High levels of sEV-AnxA2 protein and/or mRNA were associated with stage 3 and above in TNBC. Four patients who responded to neoadjuvant chemotherapy had high expression of AnxA2 protein and/or mRNA in sEVs, while other four who did not respond to chemotherapy had low levels of AnxA2 protein and mRNA in sEVs. Our data suggest that the sEV-AnxA2 protein and mRNA could be a combined predictive biomarker for responsiveness to chemotherapy in aggressive TNBC.
The Many Faces of Innate Immunity in SARS-CoV-2 Infection
(MDPI, 2021-06-04) Hanan, Nicholas; Doud, Ronnie L., Jr.; Park, In-Woo; Jones, Harlan P.; Mathew, Stephen O.
The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia. Elevated interleukin (IL)-6 and IL-8 leads to overactivity and is a prominent feature of severe COVID-19 patients. IL-6 can result in lymphopenia; where COVID-19 patients typically have significantly altered lymphocyte subsets. IL-8 attracts neutrophils; which may play a significant role in lung tissue damage with the formation of neutrophil extracellular traps leading to cytokine storm or acute respiratory distress syndrome. Several factors like pre-existing co-morbidities, genetic risks, viral pathogenicity, and therapeutic efficacy act as important modifiers of SARS-CoV-2 risks for disease through an interplay with innate host inflammatory responses. In this review, we discuss the role of the innate immune system at play with other important modifiers in SARS-CoV-2 infection.
A new approach to mentoring for research careers: the National Research Mentoring Network
(BioMed Central Ltd., 2017-12-04) Sorkness, Christine A.; Pfund, Christine; Ofili, Elizabeth O.; Okuyemi, Kolawole S.; Vishwanatha, Jamboor K.; Team, NRMN; Zavala, Maria Elena; Pesavento, Theresa; Fernandez, Mary; Tissera, Anthony; Deveci, Alp; Javier, Damaris; Short, Alexis; Cooper, Paige; Jones, Harlan P.; Manson, Spero M.; Buchwald, Dedra S.; Eide, Kristin; Gouldy, Andrea; Kelly, Erin; Langford, Nicole; McGee, Richard; Steer, Clifford J.; Unold, Thad; Weber-Main, Anne Marie; Baez, Adriana; Stiles, Jonathan; Pemu, Priscilla; Thompson, Winston; Gwathmey, Judith; Lawson, Kimberly; Johnson, Japera; Hall, Meldra; Paulsen, Douglas; Fouad, Mona; Smith, Ann; Luna, Rafael; Wilson, Donald; Adelsberger, Greg; Simenson, Drew; Cook, Abby; Feliu-Mojer, Monica; Harwood, Eileen; Jones, Amy; Branchaw, Janet; Thomas, Stephen; Butz, Amanda; Byars-Winston, Angela; House, Stephanie; McDaniels, Melissa; Quinn, Sandra; Rogers, Jenna; Spencer, Kim; Utzerath, Emily; Duplicate Of, Weber-Main; Womack, Veronica
BACKGROUND AND PURPOSE: Effective mentorship is critical to the success of early stage investigators, and has been linked to enhanced mentee productivity, self-efficacy, and career satisfaction. The mission of the National Research Mentoring Network (NRMN) is to provide all trainees across the biomedical, behavioral, clinical, and social sciences with evidence-based mentorship and professional development programming that emphasizes the benefits and challenges of diversity, inclusivity, and culture within mentoring relationships, and more broadly the research workforce. The purpose of this paper is to describe the structure and activities of NRMN. KEY HIGHLIGHTS: NRMN serves as a national training hub for mentors and mentees striving to improve their relationships by better aligning expectations, promoting professional development, maintaining effective communication, addressing equity and inclusion, assessing understanding, fostering independence, and cultivating ethical behavior. Training is offered in-person at institutions, regional training, or national meetings, as well as via synchronous and asynchronous platforms; the growing training demand is being met by a cadre of NRMN Master Facilitators. NRMN offers career stage-focused coaching models for grant writing, and other professional development programs. NRMN partners with diverse stakeholders from the NIH-sponsored Diversity Program Consortium (DPC), as well as organizations outside the DPC to work synergistically towards common diversity goals. NRMN offers a virtual portal to the Network and all NRMN program offerings for mentees and mentors across career development stages. NRMNet provides access to a wide array of mentoring experiences and resources including MyNRMN, Guided Virtual Mentorship Program, news, training calendar, videos, and workshops. National scale and sustainability are being addressed by NRMN "Coaches-in-Training" offerings for more senior researchers to implement coaching models across the nation. "Shark Tanks" provide intensive review and coaching for early career health disparities investigators, focusing on grant writing for graduate students, postdoctoral trainees, and junior faculty. IMPLICATIONS: Partners from diverse perspectives are building the national capacity and sparking the institutional changes necessary to truly diversify and transform the biomedical research workforce. NRMN works to leverage resources towards the goals of sustainability, scalability, and expanded reach.
Variations of a group coaching intervention to support early-career biomedical researchers in Grant proposal development: a pragmatic, four-arm, group-randomized trial
(BioMed Central Ltd., 2022-01-10) Weber-Main, Anne Marie; Engler, Jeffrey; McGee, Richard; Egger, Marlene J.; Jones, Harlan P.; Wood, Christine V.; Boman, Kristin; Wu, Jiqiang; Langi, Andrew K.; Okuyemi, Kolawole S.
BACKGROUND: Funded grant proposals provide biomedical researchers with the resources needed to build their research programs, support trainees, and advance public health. Studies using National Institutes of Health (NIH) data have found that investigators from underrepresented groups in the biomedical workforce are awarded NIH research grants at disproportionately lower rates. Grant writing training initiatives are available, but there is a dearth of rigorous research to determine the effectiveness of such interventions and to discern their essential features. METHODS: This 2 x 2, unblinded, group-randomized study compares the effectiveness of variations of an NIH-focused, grant writing, group coaching intervention for biomedical postdoctoral fellows and early-career faculty. The key study outcomes are proposal submission rates and funding rates. Participants, drawn from across the United States, are enrolled as dyads with a self-selected scientific advisor in their content area, then placed into coaching groups led by senior NIH-funded investigators who are trained in the intervention's coaching practices. Target enrollment is 72 coaching groups of 4-5 dyads each. Groups are randomized to one of four intervention arms that differ on two factors: [1] duration of coaching support (regular dose = 5 months of group coaching, versus extended dose = regular dose plus an additional 18 months of one-on-one coaching); and [2] mode of engaging scientific advisors with the regular dose group coaching process (unstructured versus structured engagement). Intervention variations were informed by programs previously offered by the NIH National Research Mentoring Network. Participant data are collected via written surveys (baseline and 6, 12, 18, and 24 months after start of the regular dose) and semi-structured interviews (end of regular dose and 24 months). Quantitative analyses will be intention-to-treat, using a 2-sided test of equality of the effects of each factor. An inductive, constant comparison analysis of interview transcripts will be used to identify contextual factors -- associated with individual participants, their engagement with the coaching intervention, and their institutional setting - that influence intervention effectiveness. DISCUSSION: Results of this study will provide an empirical basis for a readily translatable coaching approach to supporting the essential grant writing activities of faculty, fellows, and other research trainees, including those from underrepresented groups.
Religious service attendance and mortality among older Black men
(PLOS, 2022-09-02) Bruce, Marino A.; Beech, Bettina M.; Kermah, Dulcie; Bailey, Shanelle; Phillips, Nicole; Jones, Harlan P.; Bowie, Janice V.; Heitman, Elizabeth; Norris, Keith C.; Whitfield, Keith E.; Thorpe, Roland J.
Religious institutions have been responsive to the needs of Black men and other marginalized populations. Religious service attendance is a common practice that has been associated with stress management and extended longevity. The objective of this study was to examine the relationship between religious service attendance and all-cause mortality among Black men 50 years of age and older. Data for this study were from NHANES III (1988-1994). The analytic sample (n = 839) was restricted to participants at least 50 years of age at the time of interview who self-identified as Black and male. Mortality was the primary outcome for this study and the NHANES III Linked Mortality File was used to estimate race-specific, non-injury-related death rates using a probabilistic matching algorithm, linked to the National Death Index through December 31, 2015, providing up to 27 years follow-up. The primary independent variable was religious service attendance, a categorical variable indicating that participants attended religious services at least weekly, three or fewer times per month, or not at all. The mean age of participants was 63.6+/-0.3 years and 36.4% of sample members reported that they attended religious services one or more times per week, exceeding those attending three or fewer times per month (31.7%), or not at all (31.9%). Cox proportional hazard logistic regression models were estimated to determine the association between religious service attendance and mortality. Participants with the most frequent religious service attendance had a 47% reduction of all-cause mortality risk compared their peer who did not attend religious services at all (HR 0.53, CI 0.35-0.79) in the fully adjusted model including socioeconomic status, non-cardiovascular medical conditions, health behaviors, social support and allostatic load. Our findings underscore the potential salience of religiosity and spirituality for health in Black men, an understudied group where elevated risk factors are often present.
Enhancing research careers: an example of a US national diversity-focused, grant-writing training and coaching experiment
(BioMed Central Ltd., 2017-12-04) Jones, Harlan P.; McGee, Richard; Weber-Main, Anne Marie; Buchwald, Dedra S.; Manson, Spero M.; Vishwanatha, Jamboor K.; Okuyemi, Kolawole S.
BACKGROUND AND PURPOSE: Preparing a successful research proposal is one of the most complex skills required of professional scientists, yet this skill is rarely if ever, taught. A major goal of the National Research Mentoring Network (NRMN) in the United States (U.S.) is to support the professional advancement of postdoctoral fellows and junior faculty from diverse populations by offering intensive coaching in the development of grant proposals early in their careers. This article highlights the National Institutes of Health's (NIH) NRMN initiative to prepare diverse constituencies of early-stage biomedicine scientists for research careers by implementation of an evidence-based nationwide program of comprehensive grant writing and professional development. PROGRAM AND KEY HIGHLIGHTS: NRMN delivers four unique but complementary coaching models: the Proposal Preparation Program from the University of Minnesota (UMN); Grantwriters Coaching Groups from Northwestern University (NU); Grantwriting Uncovered: Maximizing Strategies, Help, Opportunities, Experiences from the University of Colorado Anschutz Medical Campus (UC) and Washington State University (WSU); and Steps Towards Academic Research from the University of North Texas Health Science Center (UNTHSC). Because these programs cater to scientists at different career stages, rather than employ a single approach, each is uniquely tailored to test its efficacy at the national level. The first two models prioritize scientists with reasonably well-developed research projects who are ready to write proposals for specific NIH research competitions. The other two models target postdoctoral fellows and early-career faculty who need more extensive guidance in proposal development plans. To achieve scalability, all programs also recruit faculty as Coaches-in-Training to learn approaches and acquire particular group facilitation skills required by each model. IMPLICATIONS: These efforts exemplify NRMN's potential to enhance the career development of diverse trainees on a national scale, building research skills, competitiveness for obtaining faculty positions and capacities that will result in high quality research proposals from a diverse pool of applicants, thereby advancing innovations in science and diversifying the U.S. biomedical workforce.
The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study
(Oxford University Press, 2020-09-29) Thorpe, Roland J., Jr.; Cobb, Ryon; King, Keyonna; Bruce, Marino A.; Archibald, Paul; Jones, Harlan P.; Norris, Keith C.; Whitfield, Keith E.; Hudson, Darrell
BACKGROUND AND OBJECTIVES: Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms. Few studies have investigated how AL contributes to depressive symptoms among black men. The purpose of the cross-sectional study was to examine the association between AL and depressive symptoms among middle- to old age black men. RESEARCH DESIGN AND METHODS: This project used the 2010 and 2012 wave of the Health and Retirement Study enhanced face-to-face interview that included a biomarker assessment and psychosocial questionnaire. Depressive symptoms, assessed by the endorsement of 3 or more symptoms on the Center for Epidemiological Studies-Depression 8-item scale, was the outcome variable. The main independent variable, AL, score was calculated by summing the number values that were in the high range for that particular biomarker value scores ranging from 0 to 7. black men whose AL score was 3 or greater were considered to be in the high AL group. Modified Poisson regression was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs). RESULTS: There was a larger proportion of black men in the high AL group who reported depressive symptoms (30.0% vs. 20.0%) compared with black men in the low AL group. After adjusting for age, education, income, drinking, and smoking status, the prevalence of reporting 3 or more depressive symptoms was statistically significant among black men in the high AL group (PR = 1.61 [95% CI: 1.20-2.17]) than black men in the low AL group. DISCUSSION AND IMPLICATIONS: Exposure to chronic stress is related to reporting 3 or more depressive symptoms among black men after controlling for potential confounders. Improving the social and economic conditions for which black men work, play, and pray is key to reducing stress, thereby potentially leading to the reporting of fewer depressive symptoms.

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