PIs: Ryan Williams (CCNY) / Edgar Jaimes (MSK):

Targeting Health Disparities in Onconephrology with Gene-Regulating Nanomedicine

Project Summary:

Chronic kidney disease (CKD) is an increasingly common complication of treatment in cancer survivors, especially with the advent of newer and more complex therapeutic regimens. Approximately 10% of the total US population is affected by CKD of different etiologies, including diabetes and hypertension. In African American and minority populations, CKD is 3 times more prevalent as compared to white populations. African Americans constitute 35% of patients on chronic dialysis, while representing only 13.5% of the US population. In addition to being more prevalent, CKD in African Americans is linked to a higher risk of progression to end stage kidney disease (ESKD) and is often diagnosed at later stages and undertreated as compared to whites. As a result, African Americans with CKD have worse outcomes, including increased risk for cancer. Further, there are substantial genetic causes for disparities in onco-nephrology, including hyperexpression of the cytokine TGFβ and an inherited null phenotype antioxidant enzyme GSTM1.

In prior collaborative work, the PIs have developed a kidney-targeted nanoparticle platform composed of biodegradable mesoscale nanoparticles (MNPs). These particles target the kidneys with 26-fold specificity compared to any other organ, primarily localizing in the renal tubular epithelium, the site of renal disease development. They found these particles are therapeutically effective against acute kidney injury when loaded with a free radical scavenger small molecule. However, no prior studies have investigated the use of this kidney-targeted nanoparticle to deliver targeted gene therapies, nor any therapies that focus on health disparities in onco-nephrology. In the proposed work, they will use nanoparticles that encapsulate siRNA and mRNA constructs and specifically target genetic causes of disparities in onco-nephrology. Specifically, the investigators will: 1) Evaluate the therapeutic efficacy of kidney-targeted siRNA against the fibrotic cytokine TGFβ in two rodent models of CKD; and 2) Evaluate the therapeutic efficacy of kidney-targeted mRNA encoding the antioxidant enzyme GSTM1 in two rodent models of CKD. Each target is a substantial genetic contributor to health disparities as well as urologic cancer initiation and progression. Thus, they will investigate potential for tumor formation, as well as renal function and inflammatory responses in both mouse and rat models of CKD.

PIs: Lane Gilchrist (CCNY) / Yueming Li (MSK)

Racial Disparities of Gamma-Secretase/Notch Signaling in Triple Negative Breast Cancer

Project Summary:

The overall objective of this proposal is to investigate the racial disparities of the g-secretase/Notch pathway and inhibition in triple negative breast cancer (TNBC) and provide a molecular basis for therapeutic development. The mortality from TNBC in African American (AA) women is higher than in White American (WA) or European-American (EA) women. Recent studies have indicated that Notch signaling plays an important role in this racial disparity. Notch signaling has been associated with tumor transformation, proliferation, survival, angiogenesis and metastasis. We have shown that g-secretase cleavage of Notch is highly regulated in breast cancer cells. Subtle changes in membrane lipid composition affect the distribution of Notch substrates and g-secretase and thus enzymatic activity. At this point, ethnic differences in gamma-secretase/Notch signaling and its role in the higher incidence of and poorer outcomes of AA from TNBC are poorly understood. They hypothesize that g-secretase plays a major role in the control of Notch signaling in TNBC and contributes to this racial disparity. The emergence of Notch signaling as a therapeutic target of interest in TNBC has spurred interest in this pathway as a potential suspect in the racially disparate burden in TNBC. At this point, ethnic differences in Notch signaling and its role in the higher incidence of and poorer outcomes of African-Americans from TNBC remain understudied. The project’s aims are: Aim 1: To characterize the Notch and g-secretase pathways in triple negative breast cancer (TNBC) using a panel of cell lines from African-American (AA) and European-American (EA) patients in order to examine potential racial disparities at the molecular level. Aim 2: To probe the influence of TNBC-derived lipid microenvironments on g-secretase and Notch localization and enzyme activity in supported lipid bilayer systems.

PIs: Adriana Espinosa, Carlos Riobó (CCNY) / Florence Lui, Francesca Gany (MSK)

INTERPRETing to Increase access to PSYcho-Oncology Care (INTERPRET-PSY)

Project Summary:

More than 67 million people in the U.S. speak a language other than English at home and more than 26 million are considered limited English proficient (LEP). The LEP population in the U.S. is anticipated to reach 19% of Americans by 2050. This growing and underserved population is at high risk for poor mental health outcomes in cancer survivorship: LEP cancer patients had 1.4 times the odds of reporting poor functional well-being and 1.5 times the odds of reporting major depression than their English Proficient (EP) counterparts. LEP Chinese Americans in particular lack access to needed psycho-oncology care. To address this gap, our team developed and is currently piloting Meaning-Centered Psychotherapy for Chinese patients with advanced cancer (MCP-Ch), a 6-session telehealth-delivered intervention adapted to the unique needs of Chinese cancer patients. However, bilingual Chinese-speaking mental health providers are scarce, limiting the intervention’s reach. High-quality, remotely provided medical interpretation has great potential to increase access to MCP-Ch and other psychosocial interventions for LEP cancer patients. Remote interpreting can be: (1) simultaneous (UN-style) or consecutive (interpreter waits for the speaker to finish, then interprets). Our prior research found that Remote Simultaneous Medical Interpreting (RSMI) resulted in fewer errors, better medical outcomes, and higher patient satisfaction than usual and customary methods, such as Remote Consecutive Medical Interpretation (RCMI). The objective of the proposed mixed methods pilot randomized controlled trial (RCT) is to build on our preliminary work to determine whether RSMI is feasible and acceptable to deliver in the psycho-oncology counseling context. They will assess feasibility and acceptability (Aim 1) and collect pilot data (Aim 2) on therapeutic alliance, MCP-Ch comprehension, and clinically significant interpreting errors in RSMI (n=15) vs. RCMI (n=15) vs. bilingual provider (n=15) delivery of MCP-Ch for CA cancer patients. To complement and contextualize these findings, they will conduct semi-structured interviews in a purposively sampled subset of patients in each arm (n~18 total) and their therapists (n~4) and interpreters (n~4) to identify barriers and facilitators to successful interpreter-mediated communication and outcomes (Aim 3). Study findings will be used to submit a competitive application to the National Institutes of Health to further evaluate interpreter-enabled, telehealth-delivered psychosocial interventions to LEP patients.

PIs: Lesia Ruglass (CCNY) / Jaime Ostroff (MSK)

Addressing Barriers for Seeking Lung Cancer Screening among African American at-risk for Lung Cancer

Project Summary:

Long-standing racial disparities in lung cancer mortality persist, with African Americans bearing a higher burden than their non-Hispanic European American counterparts. Despite declines in smoking prevalence, and treatment advances, lung cancer remains the deadliest cancer worldwide killing more people than breast, colorectal, prostate and cervical cancers combined. African Americans have significantly lower lung cancer survival rates and are less likely to be diagnosed early than any other racial group. Representing a major recent breakthrough, lung cancer screening with annual low-dose computed tomography (LDCT) of the chest reduces lung cancer-related mortality by identifying lung cancer at earlier, more treatable stages. Although lung cancer screening is an official recommendation, less than 6% of screening-eligible individuals have undergone screening for lung cancer that is further exacerbated by marked racial disparities in screening uptake. While screening uptake among eligible European Americans is 4.9%, screening uptake among eligible African Americans is only 1.7%. One of the leading barriers to lung cancer screening uptake is lack of awareness. The current proposal seeks to address this gap by establishing a research collaboration between MSK-CCNY investigators and others with complementary expertise in lung cancer screening and community-engaged interventions for addressing racial disparities. Building upon the highly successful community-engaged work of the Witness Project™ in promoting breast, colorectal and cervical cancer screening, our proposed collaborative pilot project will focus on adapting the highly successful Witness Project™ to address lung cancer screening barriers in the African American community. In partnership with leaders of the Witness Project™ and using a community-engaged approach and opportunities for training CCNY students, they will collect qualitative data to support the application of two promising strategies to increase adoption of lung cancer screening–a computer-tailored lung cancer screening education and decision support tool (LungTalk) and the Witness ProjectTM, a narrative breast cancer education program, for lung cancer education and screening. They will conduct focus groups with screening-eligible African American community members, lay health workers, religious leaders, clinicians, and health administrators to identify multi-level barriers and facilitators that affect lung cancer screening uptake in the African American community (Aim 1); and adapt and integrate the critical constructs of a computer-tailored lung cancer screening education and decision support tool (LungTalk) and the Witness ProjectTM, a narrative breast cancer education program, for lung cancer screening focused on the unmet needs of African American screening eligible individuals (Aim 2).

• Full: David Rumschitzki (CCNY) / Richard White (MSK): How Tumor Ensemble Models with Two Experimental Models Predict Tumor Dormancy & Reactivation in Cancers with Gender and/or Ethnic Disparities
• Full: Bao Vuong (CCNY) / Jayanta Chaudhuri (MSK): Characterizing the Role of ATM and MSH2 in Genome Stability
• Full: Gerardo Blumenkrantz (CCNY) / Abraham Aragones (MSK): Social Marketing and Technology to Increase HPV Vaccination Rates Among Mexican American Children: A Randomized Controlled Trial
• Full: Marom Bikson (CCNY) / Prasad Adusumilli (MSK): Preclinical Evaluation, Clinical Trial Preparation, and a Prospective Clinical Trail of Intraoperative Real-time Tissue Oxygenation Monitoring by Wireless Pulse Oximetry (WiPOX)
• Full: Bao Vuong (CCNY) / Jayanta Chaudhuri (MSK): Molecular Function of ATM in Class Switch Recombination
• Full: Marom Bikson (CCNY) / Govindarajan Srimathveeravalli (MSK): Framework for Non-Invasive Low Voltage Electroporation for Drug and Gene Delivery to Brain Tumors
• Full: Sihong Wang (CCNY) / Xuejun Jiang (MSK): Microfluidic Tumor Array Development and Autophagy in Cancer Treatment
• Pilot: Kevin Gardner (CCNY) / Derek Tan (MSK): Structural and chemical probing of a new anticancer target: HIF-coactivator complexes 
• Pilot: Lucas Parra (CCNY) / Sarah Eskreis-Winkler (MSK): Precision Medicine Using Unbiased Artificial Intelligence to Optimize the Use of Preoperative Breast MRI and Reduce Disparities in Outcomes
• Pilot: Deidre Anglin (CCNY) / Rosario Costas-Muñiz, Wendy Lichtenthal (MSK): Cultural Adaptation of EMPOWER for Latinx Family Caregivers in Intensive Care Units in the Context of COVID-19
• Pilot: Susannah Fritton (CCNY) / John Healey (MSK): Development of Mechanical Interventions to Enhance Drug Delivery to Bone Tumors
• Pilot: Jie Wei (CCNY) / Guang Li (MSK): Developing an Accurate and Reliable Method for Tumor Motion Monitoring
• Pilot: Tiffany Floyd (CCNY) / Katherine DuHamel (MSK): Salon-Based Intervention to Promote Colonoscopy Screening among African-American Women
• Pilot: Sihong Wang (CCNY) / Sihong Jiang (MSK) / Carlos Meriles (CCNY): Differentiating Cancer Cells by their Thermal Properties via NV Centers in Nanodiamonds
• Pilot: Pengfei Zhang (CCNY) / Jennifer Leng (MSK): TaxI Particulate matter Study (TIPS)
• Pilot: David Rumschitzki (CCNY) / Richard White (MSK): Theory & Experiment for Tumor Growth Regression and Metastasis
• Pilot: Lingyan Shi (CCNY) / Robert Alfano (CCNY) /Jason Koutcher (MSK): Early Diagnosis of Triple Negative Breast Cancer by Raman Spectroscopy and Multiphoton Microscopy
• Pilot: Itzhak Mano (CCNY) / Xuejun Jiang (MSK): Molecular Mechanisms of Regulated Necrosis in Brain Cancer: Ferroptosis & Excitotoxicity
• Pilot: Hernan Makse (CCNY) / Andrei Holodny (MSK): Graph Theoretical Analysis of Pre-operative fMRI Data in Bilingual Patients with Brain Tumors and Multiphoton Microscopy
• Pre-pilot: Ryan Williams (CCNY) / Dianna Ng (MSK): Rapid Diagnostic Evaluation of Estrogen Receptor Status in Fine Needle Aspiration Biopsies
• Pre-pilot: Steven Nicoll, Ryan Williams (CCNY) / Mark Robson (MSK): Nanocomposite hydrogels for detection and preventative hormone therapy for breast cancer