Bolden Lab Research Focus

 I believe that research is the cornerstone of any thriving academic institution and serves as a defining standard by which the excellence of a university and its faculty are evaluated. As a faculty member, I view research not only as a personal pursuit of knowledge but also as a professional obligation to students, colleagues, and the broader scientific community. I am committed to producing rigorous, theory-driven research that contributes meaningfully to both clinical practice and academic scholarship, while also nurturing the next generation of scholars.

Central to my research philosophy is a translational and interdisciplinary approach that bridges neuroscience, neurocritical care, and public health. I strive to:

• Advance theory-based research by exploring the relationships between neurocritical care management strategies and patient-centered outcomes. My goal is to develop frameworks that inform evidence-based practice and contribute to improved standards of care for individuals experiencing neurological trauma and illness.
  
  

• Foster collaborative inquiry across disciplines, institutions, and communities. I actively seek opportunities to work with clinical practitioners, biomedical scientists, public health experts, and early-career investigators. These collaborations not only enrich my own perspective but also create avenues for mentoring students and junior colleagues in research design, analysis, and dissemination.
  
  

• Integrate research into teaching by embedding emerging findings and current studies, including those under review or recently accepted for publication, into classroom discussions, case studies, and lab activities. This approach ensures that students are not only learning foundational concepts but are also being exposed to cutting-edge advancements that will shape the future of medicine and health sciences.
  
  

Ultimately, I view research as a dynamic, evolving process that informs my teaching, shapes my service, and reinforces my commitment to academic excellence. Through sustained inquiry and engagement, I aim to generate impactful knowledge that addresses real-world challenges, particularly those affecting underrepresented and medically vulnerable populations.

 As an early-career investigator, my research philosophy is rooted in a deep commitment to advancing knowledge at the intersection of neurobiology, translational medicine, and public health. I view research as both a scientific endeavor and a moral imperative, to generate findings that inform clinical practice, address health disparities, and improve the lives of vulnerable populations affected by neurological injury and disease. My research is further guided by three core principles: innovation through interdisciplinary approaches, inclusion through student mentorship and community engagement, and impact through dissemination and application.

I have developed a healthy and evolving research agenda that includes several major, interrelated streams of inquiry. Each stream is driven by a translational focus, with the long-term goal of informing therapeutic strategies for patients suffering from traumatic brain injury (TBI), glioblastoma multiforme, Alzheimer's disease. My current work is supported by competitive internal and external funding (see Research Funding section) and has laid a solid foundation for future grant submissions to NIH and other federal agencies.

1. Soluble Agonists for Enhancing Functional Recovery in Traumatic Brain Injury (TBI)

This research stream explores the therapeutic potential of targeting soluble molecules and receptor agonists to promote neural repair and restore functional outcomes following TBI. TBI continues to be a leading cause of long-term disability, yet current interventions are limited in efficacy and scope. My work investigates how bioactive compounds can be leveraged to stimulate neuroprotective signaling pathways, enhance synaptic plasticity, and mitigate secondary injury cascades.

Using both in vitro and in vivo models, I aim to characterize the molecular mechanisms by which soluble agonists influence neurovascular integrity, inflammatory signaling, and neuronal survival. This line of inquiry holds promise for identifying druggable targets and designing novel pharmacological interventions that can be rapidly translated into clinical trials. Moreover, it complements my interest in personalized medicine, as I explore how these compounds perform across diverse biological and injury contexts.

2. Astrocytes as Key Regulators of Neuroinflammation in TBI

The second major stream of my research centers on astrocytes and their dynamic role in the neuroinflammatory response following brain injury. Historically viewed as passive support cells, astrocytes are now recognized as active modulators of immune signaling, synaptic regulation, and blood-brain barrier function. My current work investigates how reactive astrocytes contribute to the pathophysiology of TBI—both as amplifiers of neuroinflammation and as potential mediators of recovery.

This research utilizes advanced cellular modeling platforms, including 3-D culture systems and iPSC-derived brain cell co-cultures, to assess astrocyte-tumor and astrocyte-injury interactions in real time. I am particularly interested in the signaling networks and metabolic shifts that govern astrocyte reactivity and phenotype plasticity. My findings will inform broader mechanistic models of neuroinflammation and support the development of astrocyte-targeted therapies to limit chronic neural damage.

This work also ties directly into my funded project, Evaluating Reactive Astrocyte Involvement in the Glioblastoma Microenvironment, and extends my expertise in glial biology to multiple domains, including neurotrauma and oncology.

3. Glioblastoma Tumor Microenvironment

My research program focuses on glioblastoma (GBM), the most aggressive primary malignant brain tumor, with an emphasis on how tumor–microenvironment interactions drive invasion, therapeutic resistance, and blood–brain barrier (BBB) dysfunction. Because GBM cells infiltrate normal brain tissue and the BBB limits effective drug delivery, my work targets the vascular interface as a critical determinant of both neurologic morbidity and treatment failure.

A central pillar of my laboratory is defining how the sorting receptor SorLA (SORL1) regulates GBM progression and microenvironmental signaling. I test the premise that SorLA influences oncogenic trafficking and survival pathways that support tumor migration and therapy resistance, and that genetic and pharmacologic modulation of SorLA can reduce invasive behavior and shift tumor–BBB interactions toward a less permissive state.

Methodologically, my lab integrates human-relevant, mechanistic model systems, including three-dimensional BBB platforms that incorporate key neurovascular unit components (brain microvascular endothelial cells, astrocytes, and pericytes) alongside GBM models. These systems enable quantitative evaluation of clinically relevant outcomes such as transendothelial migration and BBB integrity (e.g., TEER/permeability), paired with molecular readouts to define mechanisms and therapeutic targets. This research agenda is also tightly aligned with my commitment to mentorship, engaging undergraduate trainees in hypothesis-driven projects from experimental design through dissemination.

4. Inflammatory Mediators influencing Alzheimer Development

My Alzheimer’s disease and related dementias (ADRD) research program focuses on identifying modifiable, upstream drivers of cognitive decline and unequal outcomes, with a particular emphasis on populations that are historically underrepresented in brain aging research. Grounded in public health epidemiology and clinical informatics, my work examines how social, behavioral, cardiometabolic, and health-system factors converge over the life course to shape brain health trajectories.

A key component of this research investigates diagnostic pathways and delays in recognition, using longitudinal health data to characterize how individuals move through clinical care prior to ADRD identification. This includes evaluating patterns of prior neuropsychiatric diagnoses, timing of neurology/neuropsychology referral, and indicators of missed or delayed opportunities for cognitive evaluation. By mapping these trajectories, my goal is to clarify where diagnostic gaps emerge and to inform strategies that improve earlier recognition, appropriate referral, and patient-centered care.

In parallel, my program evaluates cumulative risk and resilience profiles that influence brain health outcomes. I use integrative models to quantify how cardiometabolic burden, sleep disruption, psychosocial stress/trauma, and health-system access interact to shape outcomes such as cerebrovascular events, functional limitations, and other markers of vulnerability. Complementing risk models, I also identify resilience patterns that reflect protective social and behavioral factors, with the long-term objective of informing equity-focused interventions that strengthen brain health across diverse communities.

My research is closely integrated with my teaching and mentorship activities. I actively involve undergraduate students in all phases of the research process, from experimental design to data analysis and dissemination. By incorporating elements of my active research into lectures, laboratory exercises, and summer research experiences, I aim to demystify the scientific process and inspire students—especially those from historically underrepresented backgrounds—to pursue careers in biomedical research.

I also prioritize scientific communication, community engagement, and interdisciplinary collaboration as essential components of my research philosophy. Through initiatives supported by NSF and Mellon Foundation grants, I mentor students in science communication and computational biology, further expanding the reach and impact of my scholarship.

As a principal investigator and co-investigator, I have secured a series of competitive internal and external grants that support both my foundational research in translational neuroscience and my interdisciplinary engagement with community-based public health initiatives. These awards reflect my growing research portfolio and demonstrate my capacity to lead innovative, collaborative, and impactful projects aligned with the mission of Xavier University of Louisiana.

1. Louisiana Cancer Research Consortium (LCRC) Start-Up Grant

• Title: Evaluating the Reactive Astrocyte Involvement in the Glioblastoma Microenvironment

• Role: Principal Investigator (PI)

• Funding Period: October 2023 – June 2024

This award supports preliminary investigations into the role of reactive astrocytes in shaping the glioblastoma tumor microenvironment. Using in vitro modeling and biomarker analysis, this project lays the groundwork for future proposals to NIH and other biomedical funding agencies. It also supports undergraduate student training in cellular and molecular techniques.

2. Mellon Foundation AI Innovation Grant

• Title: Genetic Engineering of DNA Mismatch Repair Mutants with Machine Learning

• Role: Principal Investigator (PI)

• Funding Period: January 2024 – August 2024

This interdisciplinary initiative combines genetics and artificial intelligence to optimize the design and analysis of DNA mismatch repair (MMR) mutants. The project integrates machine learning algorithms to predict mutational outcomes and foster innovation in molecular biology education. It also supports course-based research experiences (CUREs) to promote student engagement in computational biology.

3. National Science Foundation Scientific Communication Mini-Grant

• Title: Evaluating the Reactive Astrocyte Involvement in the Glioblastoma Microenvironment

• Role: Principal Investigator (PI)

• Funding Period: January 2024 – August 2024

This mini-grant supports public and scientific communication training linked to my glioblastoma research. It funds the development of accessible, multimedia materials designed to communicate scientific findings to broad audiences, including undergraduates, community stakeholders, and non-specialist reviewers. It contributes to my broader goal of demystifying translational neuroscience through outreach and pedagogy.

4. Louisiana Cancer Research Consortium (LCRC) Pilot Grant

• Title: Evaluating the Role of Reactive Astrocytes in the Glioblastoma Tumor Microenvironment in a 3-D System of the Blood Brain Barrier

• Role: Principal Investigator (PI)

• Funding Period: July 2024 – June 2025

This award supports preliminary investigations into the role of reactive astrocytes in shaping the glioblastoma tumor microenvironment. Using in vitro modeling and biomarker analysis, this project lays the groundwork for future proposals to NIH and other biomedical funding agencies. It also supports undergraduate student training in cellular and molecular techniques.

5.  Louisiana Biomedical Research Network Pilot Grant

• Title: 

• Role: Principal Investigator (PI)

• Funding Period: October  2024 – June 2025

TBA

6.  Louisiana Clinical & Translational Science Center Community Scholars Grant

• Title: 

• Role: Co-Principal Investigator (PI)

• Funding Period: July 2024 – June 2025

This award supports preliminary investigations into the role of reactive astrocytes in shaping the glioblastoma tumor microenvironment. Using in vitro modeling and biomarker analysis, this project lays the groundwork for future proposals to NIH and other biomedical funding agencies. It also supports undergraduate student training in cellular and molecular techniques.

University of Virginia Comprehensive Cancer Center 2025 SASCO Scholar In Residence

Initiative Two - 2025: Evaluating SorLA as a Therapeutic Target in Glioblastoma Using a 3D In Vitro BBB System

Link: https://sasco.virginia.edu/cores/#outreach-core

Title: Targeting SorLA to Inhibit Glioblastoma Invasion and Enhance Therapeutic Efficacy

Glioblastoma (GBM) is the most aggressive primary brain tumor, hallmarked by rapid proliferation, diffuse invasion, and profound resistance to standard therapies. Emerging evidence implicates the multifunctional sorting receptor SorLA in GBM pathogenesis, where it promotes tumor cell migration, survival signaling, and chemoresistance. We propose that selective pharmacological inhibition of SorLA with the small-molecule antagonist AF38469 will attenuate GBM invasion and reinforce blood–brain barrier (BBB) integrity.

To test this hypothesis, GBM cells were embedded in a three-dimensional in vitro BBB model comprising human brain microvascular endothelial cells, astrocytes and pericytes. Cultures were then treated with AF38469 at 40 nM, 400 nM, and 4 µM for 48 hours. Tumor cell invasion across the endothelial barrier was quantified by transwell migration assays, while barrier function will be measured in real time via transendothelial electrical resistance (TEER). Following treatment, single-nucleus RNA sequencing (snRNA-seq) provided details on the transcriptional shifts in both GBM and endothelial compartments to identify SorLA-dependent pathways, focusing on genes regulating extracellular matrix remodeling (e.g., MMP2/9), epithelial-to-mesenchymal transition (e.g., SNAI1, VIM), and tight junction integrity (e.g., CLDN5, OCLN).

AF38469 dose-dependently reduced GBM transmigration, preserved TEER values, and revealed downregulation of invasion-associated transcripts alongside upregulation of barrier-stabilizing genes. These findings validated SorLA as a novel therapeutic target and establish mechanistic rationale for integrating SorLA inhibitors into combinatorial GBM treatment regimens, ultimately aiming to improve patient survival.

A Studio In the Woods Scholar 2024-2025

Link: https://astudiointhewoods.org/artist/christopher-bolden/

Description: I served as a Scholar-in-Residence through Xavier University of Louisiana’s A Studio in the Woods Faculty Writing Retreat Fellowship—an Office of Academic Affairs–funded initiative administered with the Center for Teaching Advancement and Faculty Development to support faculty scholarly productivity through an intensive one- or two-week residency. The fellowship is designed to provide protected, uninterrupted time for teacher-scholars to advance major writing and research milestones, leveraging the retreat environment at A Studio in the Woods, whose mission is to preserve Mississippi River bottomland hardwood forest and provide a tranquil space where scholars can work uninterrupted.

My residency directly supported my research independence agenda in neuro-oncology by advancing the project titled “Writing Retreat: Glioblastoma Innovation.” The protected writing period was structured around two concrete scholarly deliverables: (1) completion of key components of an NIH R15 AREA proposal and (2) submission of a comprehensive review article in glioblastoma (GBM). Specifically, my retreat objectives centered on clarifying and strengthening the scientific narrative around reactive astrocytes in GBM invasion/metastasis for the R15 research strategy and synthesizing the current understanding of astrocyte involvement in GBM for the review manuscript, with the stated endpoint of submitting the review to Experimental Neurology. 

This Scholar-in-Residence experience also aligned with my mentoring and institutional impact goals. The retreat project explicitly elevated undergraduate research training and scholarly socialization by integrating Xavier students as co-authors on the review manuscript and positioning the R15 as a mechanism to expand paid research experiences and conference dissemination. The fellowship’s structure and resources (including support for residency fees, food reimbursement, and project-related materials funding) further enabled sustained progress beyond the residency itself and required reflective reporting and potential campus sharing of outcomes.