{"id":6209,"date":"2022-07-12T08:30:21","date_gmt":"2022-07-12T15:30:21","guid":{"rendered":"https:\/\/nau.edu\/center-health-equity-research\/?p=6209"},"modified":"2024-07-02T09:45:56","modified_gmt":"2024-07-02T16:45:56","slug":"making-a-difference","status":"publish","type":"post","link":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/blog\/making-a-difference\/","title":{"rendered":"Making a difference for good"},"content":{"rendered":"\n
\"Collage
From left, Archana Varadaraj, PhD, and Narendiran Rajasekaran, PhD.<\/figcaption><\/figure><\/div>\n\n\n\n

Assistant professor couple work to discover novel ways to assist American Indian and Alaska Native people through their cancer research<\/h2>\n\n\n\n

In their Cancer Biochemistry and Immunology Labs<\/a> dedicated to cancer research, Archana Varadaraj<\/strong> and Narendiran Rajasekaran<\/strong> are discovering and developing new, innovative therapies to cure treatment-resistant cancers, especially breast, renal and colorectal cancers.<\/p>\n\n\n\n

The Northern Arizona University chemistry and biochemistry power couple, both assistant professors, have dedicated their cancer research projects with the Southwest Health Equity Research Collaborative<\/a> (SHERC) to discovering real-world cancer solutions with a special focus on assisting people who are underrepresented.<\/p>\n\n\n\n

\u201cWith cancer biochemistry and immunology being new research fields at NAU, we needed to first build the infrastructure and expertise from scratch to initiate research,\u201d Varadaraj said. \u201cThis was challenging and fulfilling considering we were both early-stage investigators. Through our grants from SHERC, we were able to establish our labs with state-of-the-art infrastructure in our respective fields.\u201d<\/p>\n\n\n\n

Rajasekaran chose his SHERC research project<\/a> after discovering that colorectal cancer and breast cancer survival rates are worse for American Indian and Alaska Native people since they are more likely to be diagnosed with diseases at a later stage leading to poor treatment outcomes and increased mortality. These disparities in cancer survival rates in the American Indian and Alaska Native populations are compounded by resistance to existing therapies and high relapse rates among patients.<\/p>\n\n\n\n

\u201cCancer immunotherapy has shown promising results in patients refractory to standard chemotherapy and with a high risk of disease recurrence,\u201d Rajasekaran said. \u201cFactors within the tumor microenvironment influence the sensitivity to immunotherapy and a better understanding of the immune responses within the tumor microenvironment is important to provide new approaches in improving the efficiency of current immunotherapies.\u201d<\/p>\n\n\n\n

Varadaraj also found similar results with underrepresented populations and breast cancer.<\/p>\n\n\n\n

\u201cBreast and renal cancers disproportionately affect minority communities,\u201d Varadaraj said. \u201cA rigorous understanding of the disease informs better treatment options and personalized health care in racially disparate populations.\u201d<\/p>\n\n\n\n

Studying tissue building to prevent breast cancer<\/h3>\n\n\n\n
\"Archana<\/figure>
\n

Varadaraj created the Varadaraj Lab<\/a> at NAU to pursue her interest in understanding the tumor microenvironment of cancer, which includes blood vessels, immune and other cells, and extracellular matrix proteins. Her work specifically focuses on how the extracellular matrix proteins, which are used by the body for tissue building\u2013\u2013including collagen, fibrin, fibronectin, gelatin and other material\u2013\u2013affect diseases such as cancer through the tumor microenvironment.<\/p>\n<\/div><\/div>\n\n\n\n

\u201cIn previous work, we discovered that the matrix protein fibronectin is continuously turned over by specific cancer-promoting cytokines [secretions that cells release to communicate and interact with other cells], causing cells to alter how fibronectin is assembled,\u201d Varadaraj said.<\/p>\n\n\n\n

She said that in the same study, her team showed that breast cells that modify how it constructs fibronectin critically influence how these normal cells switch to becoming cancer cells.\nIn their SHERC-funded project, \u201cFibrillogenesis Mediated Phenotype Switching of Breast Cancer Cells<\/a>,\u201d the team addressed whether a disposition toward cancer may be driven simply by altering the assembly states of fibronectin in the absence of well-established cancer promoters.<\/p>\n\n\n\n

\u201cAlthough cancers have a well-defined genetic basis, we wanted to know if altering the microenvironment of the cancer was sufficient to arrive at a tumorigenic\/cancer state,\u201d she said.<\/p>\n\n\n\n

Their work, which resulted in the publication, \u201cFibronectin Assembly Regulates Lumen Formation in Breast Acini<\/a>,\u201d proved that factors or events that change the construction state of fibronectin in breast cells are enough to create cancer.<\/p>\n\n\n\n

\u201cWe showed for the first time that it was possible to switch normal breast cells into their cancer counterparts by preventing the assembly of fibronectin using specific inhibitory peptides in normal cells,\u201d she said.<\/p>\n\n\n\n

The team has extended some of these findings to renal cancers, specifically to understand drug resistance and to identify specific mechanisms that cause this resistant phenotype.<\/p>\n\n\n\n

\u201cWe have also extended our findings to diseases such as fibrosis, commonly associated with cancers,\u201d Varadaraj said. \u201cThis work is currently funded by the National Institutes of Health.\u201d<\/p>\n\n\n\n

Decoding the role of natural killer cells<\/h3>\n\n\n\n
\"Narendiran<\/figure>
\n

The Rajasekaran Lab<\/a> works on unraveling the role of natural killer (NK) cells, a superpower in anti-tumor immune responses, to create new forms of cancer therapies.<\/p>\n\n\n\n

Rajasekaran and his team also examine the effect of oncolytic viruses on NK cell performance. Oncolytic reoviruses are a form of immunotherapy that target and kill tumor cells, but their effect on NK cells is still unknown.<\/p>\n<\/div><\/div>\n\n\n\n

\u201cOur study establishes NK cells as strong therapeutic candidates to treat solid tumors,\u201d Rajasekaran said.<\/p>\n\n\n\n

His SHERC research project, \u201cInvestigating the Anti-tumor Cytotoxicity of Reovirus-Treated NK Cells for Cancer Therapy<\/a>,\u201d examines approaches to enhance the body\u2019s defenses against cancer.<\/p>\n\n\n\n

Results from the study were published earlier this year in the Journal of Cancer Immunology Immunotherapy titled \u201cHypoxia-inducible Factor-1 Alpha Expression is Induced by IL-2 via the PI3K\/mTOR Pathway in Hypoxic NK Cells and Supports Effector Functions in NKL Cells and Ex Vivo Expanded NK Cells<\/a>.\u201d<\/p>\n\n\n\n

\u201cThe studies have opened new avenues for the treatment of solid tumors like triple-negative breast cancer (TNBC) and renal cell carcinoma (RCC) that disproportionately affect American Indian, Alaska Native and Hispanic populations,\u201d he said.<\/p>\n\n\n\n

Rajasekaran said that future grants will focus on understanding how NK cells can be manipulated to efficiently kill tumors in hypoxic tumor microenvironments in TNBC and RCC patients.<\/p>\n\n\n\n

\u201cData from such a study will help us devise novel NK cell-based therapeutic strategies to treat these cancers in AI\/AN and Hispanic populations,\u201d Rajasekaran said.<\/p>\n\n\n\n

\n\n\n\n

This research was supported by an NIMHD center grant to the Southwest Health Equity Research Collaborative at Northern Arizona University (U54MD012388).<\/p>\n","protected":false},"excerpt":{"rendered":"

Assistant professor couple work to discover novel ways to assist American Indian and Alaska Native people through their cancer research In their Cancer Biochemistry and Immunology Labs dedicated to cancer research, Archana Varadaraj and Narendiran Rajasekaran are discovering and developing new, innovative therapies to cure treatment-resistant cancers, especially breast, renal and colorectal cancers. The Northern […]<\/p>\n","protected":false},"author":286,"featured_media":10534,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[569,570,571,155],"acf":[],"_links":{"self":[{"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/posts\/6209"}],"collection":[{"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/users\/286"}],"replies":[{"embeddable":true,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/comments?post=6209"}],"version-history":[{"count":6,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/posts\/6209\/revisions"}],"predecessor-version":[{"id":14241,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/posts\/6209\/revisions\/14241"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/media\/10534"}],"wp:attachment":[{"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/media?parent=6209"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/categories?post=6209"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/legacy.nau.edu\/center-community-health-engaged-research\/wp-json\/wp\/v2\/tags?post=6209"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}