Veltri presents PS-OC hosted talk on digital pathology and prostate cancer

Robert Veltri, associate professor Of Urology and Oncology at the Johns Hopkins School of Medicine and Director of the Fisher Biomarker Biorepository Laboratory, will  present the talk Quantitative Histomorphometry of Digital Pathology: Case study in prostate cancer,” to members of the Denis Wirtz Lab and the Johns Hopkins Physical Sciences-Oncology Center on Monday, December 9 at 2 p.m. in Croft G40 on the Homewood campus. Seating is limited.

veltri

Robert Veltri

Veltri studies the biomarkers for prostate and bladder cancer and is collaborating on applications of Quantitative Digital Image Analysis (QDIA) using microscopy to quantify nuclear structure and tissue architecture. Collaborations include Case Western Reserve University biomedical engineering and the University of Pittsburgh Electrical Engineering departments studying to assess cancer aggressiveness in prostate cancer (PCa). Furthermore,  he is studying the application of molecular biomarkers for prostate (CaP) and bladder cancer (BlCa) detection and prognosis. Veltri’s work is funded by the National Cancer Institute’s PS-OC program grant), Early Detection Research Network (EDRN), and the Department of Defense related to research on Active Surveillance for PCa. He is also a co-investigator on a SBIR-I and II grant studying the application of microtransponders to multiplex molecular urine and serum biomarker testing for CaP.  Veltri has authored over 152 scientific publications and is either inventor or co-inventor on over twenty patents and two trademarks.

In cancer fight, one sportsball-shaped particle works better than another

Apparently in the quest to treat or cure cancer, football trumps basketball. Research from the laboratory of Jordan Green, Ph.D., assistant professor of biomedical engineering at the Johns Hopkins University School of Medicine, has shown that elliptical football-shaped microparticles do a better job than basketball-shaped ones in triggering an immune response that attacks cancer cells.

football particles-greenGreen collaborated with Jonathan Schneck, M.D., Ph.D., professor of pathology, medicine and oncology. Both are affiliated faculty members of Johns Hopkins Institute for NanoBioTechnology. Their work was published in the journal Biomaterials on Oct 5.

The particles, which are essentially artificial antigen presenting cells (APCs), are dotted with tumor proteins (antigens) that signal trouble to the immune response. It turns out that flattening the spherical particles into more elliptical, football-like shapes provides more opportunities for the fabricated APCs to come into contact with cells, which helps initiate a stronger immune response.

If you think about it, this makes sense. You can’t tackle someone on the basketball court the way you can on the gridiron.

Read the Johns Hopkins press release here:

FOOTBALL-SHAPED PARTICLES BOLSTER THE BODY’S DEFENSE AGAINST CANCER

Read the journal article here:

Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells

ChemBE seminar focuses on cancer research innovation

The Department of Chemical and Biomolecular Engineering’s  scheduled Thursday, October 10 seminar will continue as planned at 3:30 PM in Maryland Hall 110. Jerry Lee, the Health Sciences Director at the National Cancer Institute (National Institutes of Health) will present his lecture “Advancing Convergence and Innovation in Cancer Research: National Cancer Institute Center for Strategic Scientific Initiatives (CSSI).”  A small reception will follow in Maryland Hall 109.

Jerry Lee

Jerry S.H. Lee, Ph.D

ABSTRACT

The National Cancer Institute (NCI) Center for Strategic Scientific Initiatives (CSSI) is a component of the NCI’s Office of the Director focused on emerging advanced technologies that have the potential of uniquely impacting the full spectrum of cancer basic and clinical research. The Center is tasked with planning, developing, executing, and implementing rapid strategic scientific and technology initiatives that keep the Institute ahead of the scientific curve with respect to potential new exciting areas and discoveries. This may involve direct development and application of advanced technologies, synergy of large scale and individual initiated research, and/or using available federal mechanisms to forge novel partnerships that emphasize innovation, trans-disciplinary teams and convergence of scientific disciplines. With an emphasis on complementing the scientific efforts of other NCI divisions, CSSI’s efforts seek to enable the translation of discoveries into new interventions, both domestically and in the international arena, to detect, prevent and treat cancer more effectively. This presentation will highlight various programs and their associated accomplishments within CSSI’s broad scientific portfolio of programs (Clinical Proteomic Tumor Analysis Consortium, Alliance for Nanotechnology in Cancer, Physical Sciences-Oncology Centers, Innovative Molecular Analysis Technologies, and Provocative Questions) and describe future directions and opportunities.

Game Theory and Cancer

What does game theory and cancer have to do with each other. I am not sure but this interesting workshop hosted by the Princeton Physical Sciences-Oncology Center and Johns Hopkins University might help you figure that out.

An announcement about the event reads:

Screen Shot 2013-08-02 at 12.03.06 PMRegistration is now open for the Workshop on Game Theory and Cancer, scheduled on August 12-13 in Baltimore, MD, and jointly hosted by our Princeton PS-OC and Johns Hopkins University. The main goal of this workshop is to provide a dialogue between leading basic researchers and clinical investigators that would help make headway against the very stubborn problem of cancer, and to jolt the oncology community into confronting the serious clinical problems that have previously been avoided.

The flyer is pretty cool, too.  Check it out here.

Additional information and preliminary agenda can be found at: http://www.princeton.edu/psoc/training/

To register, please go to: https://prism.princeton.edu/ps-oc/regform.php

For questions about the event, email maranzam@princeton.edu or sclam@princeton.edu

Landmark physical characterization of cancer cells completed

An enormous collaborative effort between a multitude of academic and research centers has characterized numerous physical and mechanical properties on one identical human cancer cell line. Their two-year cooperative study, published online in the April 26, 2013 journal Science Reports, reveals the persistent and agile nature of human cancer cells as compared to noncancerous cells. It also represents a major shift in the way scientific research can be accomplished.

Human breast cancer cells like these were used in the study. (Image created by Shyam Khatau/ Wirtz Lab)

Human breast cancer cells like these were used in the study. (Image created by Shyam Khatau/ Wirtz Lab)

The research, which was conducted by 12 federally funded Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute, is a systematic comparison of metastatic human breast-cancer cells to non-metastatic breast cells that reveals dramatic differences between the two cell lines in their mechanics, migration, oxygen response, protein production and ability to stick to surfaces. They have also discovered new insights into how human cells make the transition from nonmalignant to metastatic, a process that is not well understood.

Denis Wirtz, a Johns Hopkins professor of chemical and biomolecular engineering with joint appointments in pathology and oncology who is the corresponding author on the study, remarked that the work adds a tremendous amount of information about the physical nature of cancer cells. “For the first time ever, scientists got together and have created THE phenotypic signature of cancer” Wirtz said. “Yes, it was just one metastatic cell line, and it will require validation with many other cell lines. But we now have an extremely rich signature containing many parameters that are distinct when looking at metastatic and nonmetastatic cells.”

Wirtz, who directs the Johns Hopkins Physical Sciences-Oncology Center, also noted the unique way in which this work was conducted: all centers used the same human cell line for their studies, which makes the quality of the results unparalleled. And, since human and not animal cells were used, the findings are immediately relevant to the development of drugs for the treatment of human disease.

“Cancer cells may nominally be derived from the same patient, but in actuality they will be quite different because cells drift genetically over just a few passages,” Wirtz said.  “This makes any measurement on them from different labs like comparing apples and oranges.” In this study, however, the genetic integrity of the cell lines were safeguarded by limiting the number times the original cell cultures could be regrown before they were discarded.

The nationwide PS-OC brings together researchers from physics, engineering, computer science, cancer biology and chemistry to solve problems in cancer, said Nastaran Zahir Kuhn, PS-OC program manager at the National Cancer Institute.

“The PS-OC program aims to bring physical sciences tools and perspectives into cancer research,” Kuhn said. “The results of this study demonstrate the utility of such an approach, particularly when studies are conducted in a standardized manner from the beginning.”

For the nationwide project, nearly 100 investigators from 20 institutions and laboratories conducted their experiments using the same two cell lines, reagents and protocols to assure that results could be compared. The experimental methods ranged from physical measurements of how the cells push on surrounding cells to measurements of gene and protein expression.

“Roughly 20 techniques were used to study the cell lines, enabling identification of a number of unique relationships between observations,” Kuhn said.

Wirtz added that it would have been logistically impossible for a single institution to employ all of these different techniques and to measure all of these different parameters on just one identical cell line. That means that this work accomplished in just two years what might have otherwise taken ten, he said.

The Johns Hopkins PS-OC made specific contributions to this work. Using particle-tracking microrheology, in which nanospheres are embedded in the cell’s cytoplasm and random cell movement is visually monitored, they measured the mechanical properties of cancerous versus noncancerous cells. They found that highly metastatic breast cancer cells were mechanically softer and more compliant than cells of less metastatic potential.

Using 3D cell culturing techniques, they analyzed the spontaneous migratory potential (that is, migration without the stimulus of any chemical signal) of cancerous versus noncancerous cells. They also analyzed the extracellular matrix molecules that were deposited by the two cell lines and found that cancerous cells deposited more hyaluronic acid (HA). The HA, in turn, affects motility, polarization and differentiation of cells.  Finally, the Hopkins team measured the level of expression of CD44, a cell surface receptor that recognizes HA, and found that metastatic cells express more CD44.

The next steps, Wirtz said, would be to validate these results using other metastatic cell lines.  To read the paper, which is published in an open access journal, follow this link: http://www.nature.com/srep/2013/130422/srep01449/full/srep01449.html

Excerpts from original press release by Princeton science writer Morgan Kelly were used.

 

 

 

 

Recent publications from the Johns Hopkins Physical Sciences-Oncology Center

Johns Hopkins Physical Sciences-Oncology Center has had a productive quarter publishing from February to May 2013. Here are some of the most recent publications in support or the center’s core research projects, including a huge collaborative work drawing on the knowledge and research findings of the entire PS-OC network.

Screen Shot 2013-05-15 at 4.27.37 PMThat paper, A physical sciences network characterization of non-tumorigenic and metastatic cells, was the work of 95 authors from all 12 of the National Cancer Institute’s PS-OC  program centers. JHU’s PS-OC director Denis Wirtz, the Theophilus H. Smoot Professor in the Johns Hopkins Department of Chemical and Ciomolecular Engineering, is the corresponding author on this massive effort. We will be discussing the findings of that paper in a future post here on the PS-OC website. Until then, here is a link to that network paper and 13 other recent publications from the Johns Hopkins PS-OC.

  • A physical sciences network characterization of non-tumorigenic and metastatic cells.Physical Sciences – Oncology Centers Network, Agus DB, Alexander JF, Arap W,Ashili S, Aslan JE, Austin RH, Backman V, Bethel KJ, Bonneau R, Chen WC,Chen-Tanyolac C, Choi NC, Curley SA, Dallas M, Damania D, Davies PC, Decuzzi P,Dickinson L, Estevez-Salmeron L, Estrella V, Ferrari M, Fischbach C, Foo J,Fraley SI, Frantz C, Fuhrmann A, Gascard P, Gatenby RA, Geng Y, Gerecht S,Gillies RJ, Godin B, Grady WM, Greenfield A, Hemphill C, Hempstead BL, HielscherA, Hillis WD, Holland EC, Ibrahim-Hashim A, Jacks T, Johnson RH, Joo A, Katz JE,Kelbauskas L, Kesselman C, King MR, Konstantopoulos K, Kraning-Rush CM, Kuhn P,Kung K, Kwee B, Lakins JN, Lambert G, Liao D, Licht JD, Liphardt JT, Liu L, LloydMC, Lyubimova A, Mallick P, Marko J, McCarty OJ, Meldrum DR, Michor F,Mumenthaler SM, Nandakumar V, O’Halloran TV, Oh S, Pasqualini R, Paszek MJ,Philips KG, Poultney CS, Rana K, Reinhart-King CA, Ros R, Semenza GL, Senechal P,Shuler ML, Srinivasan S, Staunton JR, Stypula Y, Subramanian H, Tlsty TD, TormoenGW, Tseng Y, van Oudenaarden A, Verbridge SS, Wan JC, Weaver VM, Widom J, Will C, Wirtz D, Wojtkowiak J, Wu PH.  Sci Rep. 2013 Apr 25;3:1449. doi:10.1038/srep01449. PubMed PMID: 23618955; PubMed Central PMCID: PMC3636513. http://www.ncbi.nlm.nih.gov/pubmed/23618955
  • Procollagen Lysyl Hydroxylase 2 Is Essential for Hypoxia-Induced Breast Cancer Metastasis. Gilkes DM, Bajpai S, Wong CC, Chaturvedi P, Hubbi ME, Wirtz D, Semenza GL.Mol Cancer Res. 2013 May 7. [Epub ahead of print] PubMed PMID: 23378577. http://www.ncbi.nlm.nih.gov/pubmed/23378577
  • Predicting how cells spread and migrate: Focal adhesion size does matter. Kim DH, Wirtz D. Cell Adh Migr. 2013 Apr 29;7(3). [Epub ahead of print] PubMed PMID: 23628962. http://www.ncbi.nlm.nih.gov/pubmed/23628962
  • Hypoxia-inducible Factor 1 (HIF-1) Promotes Extracellular Matrix Remodeling under Hypoxic Conditions by Inducing P4HA1, P4HA2, and PLOD2 Expression in Fibroblasts. Gilkes DM, Bajpai S, Chaturvedi P, Wirtz D, Semenza GL. J Biol   Chem. 2013 Apr 12;288(15):10819-29. doi: 10.1074/jbc.M112.442939. Epub 2013 Feb 19. PubMed PMID: 23423382; PubMed Central PMCID: PMC3624462. http://www.ncbi.nlm.nih.gov/pubmed/23423382
  • Perivascular cells in blood vessel regeneration. Wanjare M, Kusuma S, Gerecht S. Biotechnol J. 2013 Apr;8(4):434-47. doi: 10.1002/biot.201200199. PubMed PMID: 23554249. http://www.ncbi.nlm.nih.gov/pubmed/23554249
  • Focal adhesion size uniquely predicts cell migration. Kim DH, Wirtz D. FASEB J. 2013 Apr;27(4):1351-61. doi: 10.1096/fj.12-220160. Epub 2012 Dec 19. PubMed PMID: 23254340; PubMed Central PMCID: PMC3606534. http://www.ncbi.nlm.nih.gov/pubmed/23254340
  • Notch4-dependent Antagonism of Canonical TGFβ1  Signaling Defines Unique Temporal Fluctuations of SMAD3 Activity in Sheared Proximal Tubular Epithelial Cells. Grabias BM, Konstantopoulos K. Am J Physiol Renal Physiol. 2013 Apr 10. [Epub ahead of print] PubMed PMID: 23576639. http://www.ncbi.nlm.nih.gov/pubmed/23576639
  • Integration and regression of implanted engineered human vascular networks during deep wound healing. Hanjaya-Putra D, Shen YI, Wilson A, Fox-Talbot K, Khetan S, Burdick JA, Steenbergen C, Gerecht S. Stem Cells Transl Med. 2013 Apr;2(4):297-306. doi: 10.5966/sctm.2012-0111. Epub 2013 Mar 13. PubMed PMID: 23486832. http://www.ncbi.nlm.nih.gov/pubmed/23486832
  • Collagen Prolyl Hydroxylases are Essential for Breast Cancer Metastasis. Gilkes DM, Chaturvedi P, Bajpai S, Wong CC, Wei H, Pitcairn S, Hubbi ME, Wirtz D, Semenza GL. Cancer Res. 2013 Mar 28. [Epub ahead of print] PubMed PMID: 23539444. http://www.ncbi.nlm.nih.gov/pubmed/23539444
  • Simultaneously defining cell phenotypes, cell cycle, and chromatin modifications at single-cell resolution.Chambliss AB, Wu PH, Chen WC, Sun SX, Wirtz D.FASEB J. 2013 Mar 28. [Epub ahead of print] PubMed PMID: 23538711.http://www.ncbi.nlm.nih.gov/pubmed/23538711
  • Interstitial friction greatly impacts membrane mechanics. Wirtz D. Biophys J.2013 Mar 19;104(6):1217-8. doi: 10.1016/j.bpj.2013.02.003. Epub 2013 Mar 19.PubMed PMID: 23528079; PubMed Central PMCID: PMC3602747.http://www.ncbi.nlm.nih.gov/pubmed/23528079
  • Functional interplay between the cell cycle and cell phenotypes. Chen WC, Wu PH, Phillip JM, Khatau SB, Choi JM, Dallas MR, Konstantopoulos K,Sun SX, Lee JS, Hodzic D, Wirtz D.Integr Biol (Camb). 2013 Mar;5(3):523-34. doi:10.1039/c2ib20246h. PubMed PMID: 23319145 http://www.ncbi.nlm.nih.gov/pubmed/23319145
  • High-throughput secretomic analysis of single cells to assess functional cellular heterogeneity. Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, Fan R. Anal Chem. 2013 Feb 19;85(4):2548-56. doi:10.1021/ac400082e. Epub 2013 Feb 1. PubMed PMID: 23339603; PubMed Central PMCID:  PMC3589817.http://www.ncbi.nlm.nih.gov/pubmed/23339603\

 

Self-assembling drug molecules could fight cancer

A popular method of targeted drug delivery for anti-cancer drugs involves doping another material with the desired pharmaceutical to obtain better targeting efficiency to tumor sites. The problem with this method, researchers have discovered, is that the quantity of drug payload per delivery unit can vary widely and that the materials used for delivery can have toxic side effects.

But what if you could turn the drug molecule itself into a nanoscale delivery system, cutting out the middleman completely?

TEM image of nanotubes formed by self-assembly of an anticancer drug amphiphile. These nanotubes possess a fixed drug loading of 38% (w/w). Image from Cui Lab.

TEM image of nanotubes formed by self-assembly of an anticancer drug amphiphile. These nanotubes possess a fixed drug loading of 38% (w/w). Image from Cui Lab.

Using the process of molecular self-assembly, that is what Honggang Cui, an assistant professor in the Department of Chemical and Biomolecular Engineering at Johns Hopkins University, is attempting to do. His efforts have netted him the prestigious Faculty Early Career Development (CAREER) Award from the National Science Foundation. Cui, an affiliated faculty member of the Johns Hopkins Institute for NanoBioTechnology, will receive the $500,000 award over five years.

Cui explained that a current method of delivering anti-cancer drugs is to enclose them in a nanoscale carrier made of natural or synthetic materials, but this method presents several challenges. “The amount of drug loaded per carrier is very much limited and varies from batch to batch. Even in the same batch, there is a drug loading variation from carrier to carrier. Additionally, the carrier material itself may have toxic side effects,” he said.

Cui’s research seeks to eliminate the need for the carrier by coaxing the drug molecules themselves to form their own carrier through the process of self-assembly. His team is developing new molecular engineering strategies to assemble anti-cancer drugs into supramolecular nanostructures.

“Such supramolecules could carry as much as 100 percent of the drug, would possess a fixed amount of drug per nanostructure and would minimize the potential toxicity of the carrier,” Cui said.

To learn more about research in the Cui lab go to http://www.jhu.edu/cui/

 

Molecular culprit linked to breast cancer spread

Johns Hopkins researchers have uncovered a protein “partner” commonly used by breast cancer cells to unlock genes needed for spreading the disease around the body. A report on the discovery, published Nov. 5 on the website of the Proceedings of the National Academy of Sciences, details how some tumors get the tools they need to metastasize.

“We’ve identified a protein that wasn’t known before to be involved in breast cancer progression,” says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and director of the Vascular Program at the university’s Institute for Cell Engineering. “The protein JMJD2C is the key that opens up a whole suite of genes needed for tumors to grow and metastasize, so it represents a potential target for cancer drug development.” Semenza also is associate director of the Johns Hopkins Physical Sciences-Oncology Center.

Semenza and his colleagues made their finding when they traced the activity of HIF-1, a protein known to switch on hundreds of genes involved in development, red blood cell production, and metabolism in normal cells. Previous studies had shown that HIF-1 could also be hijacked to switch on genes needed to make breast tumors more malignant.

Would-be tumor cells face a host of challenges as they make the transition from working with their host to working against it, such as the need to evade the immune system and to produce more cancer cells, explains Weibo Luo, Ph.D., an instructor in the Institute for Cell Engineering and Department of Biological Chemistry who led the project. All of these efforts require switching on the right genes for the job.

To learn more about how HIF-1 works, the researchers tested a range of human proteins to see whether they would interact with HIF-1. They then sifted through the 200 resulting hits, looking for proteins involved in chemical changes to sections of DNA that determine whether or not the genes they contain are available for use. “In order for HIF-1 to switch genes on, they have to be available, but many of the genes HIF-1 activates are normally locked down in mature cells,” explains Luo. “So we thought HIF-1 must have a partner that can do the unlocking.”

That partner turned out to be JMJD2C, Luo says. Delving deeper, the researchers found that HIF-1 switches on the JMJD2C gene, stimulating production of the protein. HIF-1’s presence also enables JMJD2C to bind to DNA at other HIF-1 target genes, and then loosen those DNA sections, enabling more HIF-1 to bind to the same sites and activate the target genes.

To test the implications of their discovery, the research team injected mice with breast cancer cells in which the JMJD2C protein was not produced. Tumors with depleted JMJD2C were much less likely to grow and metastasize to the lungs, confirming the protein’s role in breast cancer progression, says Luo.

“Active HIF proteins have been found in many types of tumors, so the implications of this finding go beyond breast cancer,” says Luo. “JMJD2C is both an important piece of the puzzle of how tumors metastasize, and a potential target for anti-cancer therapy.”

Other authors of the research report are Ryan Chang, Jun Zhong, Ph.D., and Akhilesh Pandey, M.D., Ph.D., all of the Johns Hopkins University School of Medicine.

This work was supported by grants from the National Heart, Lung, and Blood Institute (contracts N01-HV28180 and HHS-N268201000032C), and by funds from the Johns Hopkins Institute for Cell Engineering.

On the Web:

Johns Hopkins Physical Sciences-Oncology Center: http://psoc.inbt.jhu.edu/

Link to article: http://www.pnas.org/content/early/2012/10/31/1217394109.abstract

Semenza lab: http://www.hopkinsmedicine.org/institute_cell_engineering/experts/gregg_semenza.html

Q&A with Semenza: http://www.hopkinsmedicine.org/institute_cell_engineering/experts/meet_scientists/gregg_semenza.html

Original press release by Shawna WilliamsCatherine Kolf and Vanessa McMains

 

 

Cancer data stored in the cloud could improve treatments

These days, storing photos or music remotely in “the cloud”  has become common place. Now Johns Hopkins researchers are applying the concept to the storage of medical data in the hopes of predicting and improving cancer patient treatments and outcomes.

Images courtesy Denis Wirtz/JHU

“The long-range goal is to make these data available through the Internet to physicians who are diagnosing and treating cancer patients around the world,” said Denis Wirtz , associate director of the Johns Hopkins Institute for NanoBioTechnology and professor of chemical and biomolecular engineering. Using a $3.75 million grant over five years from the National Cancer Institute Common Fund Single Cell Analysis Program, Wirtz launched the program in October, with two colleagues from the Johns Hopkins School of Medicine, Anirban Maitra and Ralph Hruban.

Initially the database will focus on information from pancreatic cancer patient cell lines but will expand to other types of cancer, including ovarian.  Data gathered and stored will be at the single cell level, which Wirtz explains, provides better information for predicting how individual patients may respond to certain drugs. Drugs that work well for one patient may do nothing at all, or even be harmful, for another, Wirtz said. Understanding and predicting these outcomes before treatment is a step toward more personalized medicine, he added.

To read more about “cloud pathology,” go to the press release issued by John Hopkins University.

Johns Hopkins Institute for NanoBioTechnology

Johns Hopkins Engineering in Oncology Center

Johns Hopkins Kimmel Cancer Center

 

Konstantopoulos named BMES fellow

Konstantinos Konstantopoulos (Photo by Mary Spiro)

Konstantinos Konstantopoulos, professor and chair of the Department of Chemical and Biomolecular Engineering at Johns Hopkins University’s Whiting School of Engineering has been named a Fellow of the Biomedical Engineering Society (BMES). Konstantopoulos was one of only nine fellows elected to the Society’s Class of 2012.

BMES states that Konstantopoulos received this honor in recognition of his “seminal bioengineering research contributions involving the discovery and characterization of novel selectin ligands expressed by metastatic tumor cells.”  Formal installation of fellows will take place at the BMES annual meeting  October 24-27 in Atlanta.

Konstantopoulos is an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology. He is also a project leader with the Johns Hopkins Physical Sciences-Oncology Center. Together with Martin Pomper, a School of Medicine professor of radiology and co-principal investigator of the Johns Hopkins Center of Cancer Nanotechnology Excellence, Konstantopoulos is researching mechanochemical effects on metastasis.

Specifically, his work investigates the effects of fluid mechanical forces at different oxygen tension microenvironments on tumor cell signaling, adhesion and migration. Fluid flow in and around tumor tissue modulates the mechanical microenvironment, including the forces acting on the cell surface and the tethering force on cell-substrate connections. Cells in the interior of a tumor mass experience a lower oxygen tension microenvironment and lower fluid velocities than those at the edges in proximity with a functional blood vessel, and are prompted to produce different biochemical signals. These differential responses affect tumor cell fate that is, whether a cell will live or die, and whether it will be able to detach and migrate to secondary sites in the body.

According to the BMES website, members who demonstrate exceptional achievements and experience in the field of biomedical engineering, as well as a record of membership and participation in the Society, have the opportunity to become fellows. Fellows are selected and conferred  by the BMES board of directors through a highly selective process. Nominations for each of these categories may be made by Society members and the board of directors.

Learn more about research in the Konstantopoulos Lab here.