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Brown Lab awarded NSF grant to study the impact of collagen properties on tumor locomotion

Wednesday, June 1, 2022

Congratulations to the Brown Lab for a 3-year NSF grant entitled “Collaborative Research: Microenginered tumor-mimetic collagen landscapes to test the role of prognostic structural cues on cell migration through the extracellular matrix.” In this project the Brown Lab will collaborate with Dr. Vinay Abhyankar of RIT, holder of a linked grant, to explore the relationships between collagen fiber internal structure, overall orientation, and tumor cell motility patterns. This project is the result of Dr. Brown’s work exploring the use of collagen fiber orientation as a clinical prognostic of metastatic outcome, and Dr. Abhyankar’s work developing collagen gels with tunable orientation characteristics.

Brown Lab awarded Wilmot grant to quantify the effect of patient race on an optical predictor of metastatic outcome

Saturday, January 1, 2022

The Brown Lab is proud to have been awarded a Wilmot Center of Excellence Community Pilot Project award entitled “Differences in a prognostic signature of metastasis among ethnic groups.” This project arises from the Brown Lab’s discovery that collagen fiber internal structure, as quantified by the directionality of Second Harmonic light scattering, is an independent prognostic indicator of metastasis-free survival time. The primary goal of the project is to fully quantify the differences in this and other prognostic indicators of metastasis among racial groups.

Brown Lab receives SPIN grant to fund collaboration with Majewska Lab exploring impact of microglia on brain ECM

Wednesday, September 1, 2021

The Brown Lab, in collaboration with the laboratory of Dr. Ania Majewska of the URMC Department of Neuroscience, is proud to have been awarded a Schmitt Program in Integrative Neuroscience (SPIN) grant entitled “Interactions between microglial dynamics and the brain extracellular matrix.” The primary goal of the project is to quantify the effect of microglial activity on the diffusive hindrance of the brain ECM. This project exploits the Brown Lab’s history of development and application of novel methods to quantify diffusive transport in tissues, and the Majewska Lab’s exploration of the role of microglia in learning and memory.

BME PhD candidate Danielle Desa awarded 2019 Research Initiative grant

Monday, May 20, 2019

Congratulations to Danielle Desa, a third-year biomedical engineering PhD student in the lab of Professor Ed Brown, who has received a 2019 Research Initiative grant from the Breast Cancer Coalition of Rochester.

Danielle was awarded the Pre-Doctoral Grant to support her proposal, "Understanding the Mechanisms Underlying a Novel Predictor of Metastasis." She will investigate how the way light scatters off fibrillar collagen, a protein in the space between healthy cells through which tumor cells move, helps predict metastasis in certain breast cancers. Danielle will develop a tumor model free of other cell types, which will allow her to focus on the relationship between cell motility and the collagen properties affecting light scattering. The data from her study will be used for more complex experiments that could lead to the development of new therapies to prevent metastatic disease.

Danielle holds a Bachelor of Science degree in physics and mathematics from Creighton University and a Master of Science degree in biomedical engineering from University of Rochester. She received numerous awards as an undergraduate, including the University of Nebraska Medical Center Outstanding Undergraduate Research Award, and was named a Clare Booth Luce Research Scholar by the Henry Luce Foundation. She has contributed to several presentations at the Biomedical Optics Congress, the Annual Biomedical Engineering Society Meeting, and the United States and Canadian Academy of Pathology Annual Meeting.

Ed Brown works with Marvin Doyley on Tissue Stiffness is a Mosh Pit Where Cancer Cells Thrive

Thursday, December 6, 2018

Imagine being at a packed concert hall with a mosh pit full of dancers creating a wall against outsiders. When targeted drugs try to make their way toward a pancreas tumor, they encounter a similar obstacle in stiff tissue that surrounds and protects the cancer.

A new University of Rochester study demonstrates how imaging technology can be used to accurately measure tissue stiffness — thereby predicting the likelihood that drugs will be able get through to the tumor and guide drug penetration.

"Being able to 'see' stiff tissue in the tumor microenvironment is a detection strategy that could help oncologists plan treatments for their patients and monitor progress," said senior author Marvin Doyley, Ph.D.

A medical physicist and associate professor of Electrical and Computer Engineering and Biomedical Engineering, Doyley is collaborating with David Linehan, M.D., director of clinical operations at UR Medicine's Wilmot Cancer Institute, and a surgeon/scientist who also has a special interest in pancreatic cancer. For years Linehan has been investigating the critical role the microenvironment plays in promoting pancreas tumors, and he has designed clinical trials for drugs that stimulate the immune system to attack pancreas tumors.

Their collaboration recognizes that chemotherapy followed by surgery is currently the best treatment, and therefore reducing tissue stiffness is critical for that goal.

Doyley and Linehan are seeking funding to continue the investigation in humans. They would like to confirm that ultrasound technology can be used effectively to guide drug delivery; their team is also working with Wilmot scientist Edward Brown, Ph.D., an associate professor of Biomedical Engineering, who studies the collagen-rich fibers near tumors that contribute to tissue stiffness and cancer metastasis.

Read More: Ed Brown works with Marvin Doyley on Tissue Stiffness is a Mosh Pit Where Cancer Cells Thrive

Professor Ed Brown receives NIH grant for research project, "Using Second Harmonic Generation to Predict Metastatic Outcome in Colon Adenocarcinoma"

Monday, March 20, 2017

Professor Edward Brown has received NIH funding for his research project titled, "Using Second Harmonic Generation to Predict Metastatic Outcome in Colon Adenocarcinoma."

"In summary, we previously discovered that an optical scattering phenomenon from primary tumor samples provides an independent prognostic indicator of time to metastasis in colon cancer patients," Professor Brown says. "With this grant we will explore if and how this can be used to improve prediction of outcomes for individual patients, leading to improved therapy decisions."

Abstract:

When treating a colon adenocarcinoma (CA) patient, after surgical resection of the tumor the clinician must formulate a plan for adjuvant systemic therapy. This decision is based upon an assessment of the risk of systemic disease recurrence, and is currently informed by pathological factors such as stage, histological grade, and lymph node status. Improvement of the accuracy of risk assessment for individual patients is an area of recognized need. Much of the current information used to assess risk focuses on the cells within tumors, including their morphological properties. Less attention is paid to the extracellular matrix through which metastasizing cells must travel. Second harmonic generation (SHG) is an optical scattering phenomenon whose directionality (as quantified by the "F/B" ratio) is affected by the diameter, spacing, and disorder of fibrils within collagen fibers. Our preliminary data suggests that F/B analysis of tumor samples provides prognostic information about future metastasis that is "matrix-focused" and hence complementary to current "cell-focused" methods. Consequently we hypothesize that F/B is a clinically useful predictor of metastatic outcome in colon adenocarcinoma. In a preliminary study in 44 Stage I colon adenocarcinoma samples we found that F/B of the primary tumor is a significant prognostic indicator of progression free survival time. Significantly, the quartile of patients with the lowest F/B ratio had a 15 year progression free survival percentage of below 50%. In other words, in this study F/B could identify a subset of Stage I patients who had survival statistics similar to Stage III patients. Stage I patients are rarely prescribed adjuvant chemotherapy while Stage III patients are almost always prescribed it. This suggests that F/B can identify patients who would have benefitted from adjuvant chemotherapy and who were left untreated based upon current prognostic indicators. The prognostic trend was also evident in a cohort of 72 Stage II colon adenocarcinoma samples, although it was not significant. This project will move this idea closer to the clinic by first (Aim 1) using archived samples and follow up data in separate training and validation sets to develop predictive algorithms that include F/B, in addition to clinical and genomic information. Second it will (Aim 2) quantify the effect of adjuvant chemotherapy on the predictive ability of the algorithms, as well as quantify their ability to predict chemotherapeutic efficacy. We predict that F/B analysis will be an effective tool that can reach the clinic rapidly after this study to improve metastatic risk assessment. Improving the accuracy of risk estimation for an individual patient will allow clinicians to treat those patients who are destined for metastases, improving outcomes, while avoiding treatment for those patients who are not, reducing overtreatment.

Brown Lab secures BCRP grant to understand mechanisms of metastasis predictor

Sunday, January 1, 2017

Congratulations to the Brown Lab for a Department of Defense Breast Cancer Research Program (BCRP) Breakthrough Grant entitled “Understanding the Role of Matrix Microstructure in Metastasis.” The goal of this grant is to evaluate molecular mechanisms underlying the ability of Second Harmonic Generation (SHG) directionality to predict metastatic outcome in patient samples. In collaboration with Dr. Catherine Kuo of the University of Rochester BME Department, holder of a linked grant, they will understand how scattering directionality is related to collagen properties, and what parameters influence directionality modifications by tumor cells. This work builds on Dr. Brown’s previous exploration of the ability of SHG directionality to predict metastatic outcome, and Dr. Kuo’s investigation of collagen material properties.