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Finkielstein Lab

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THE FINKIELSTEIN LAB:
Integrated Cellular Responses Lab

     

     

Led by principal investigator Carla Finkielstein, Ph.D., the Integrated Cellular Responses Lab studies studies the molecular clocks that tell cells when it’s time to grow, divide, and die. Cells in our body have a predictable 24-hour cycle of division that is regulated by a mix of genetic and environmental cues, such as exposure to light, temperature, and hormone levels. The Finkielstein Lab offers a critical foundation for the emerging field of chronotherapeutics – the study of time-of-day medicine. This new discipline integrates the cellular and molecular biology of circadian rhythms to inform decision-making about when a therapeutic should be administered to yield the best results. 

Most of the cancer malignancies arise from malfunction of genes that control the cellular responses to DNA-damage as well as cell growth and division. The fact that cancer results from the combined action of multiple oncogenic alterations argues that single-agent therapies will remain the exception. The identification of appropriate targets is based on a detailed understanding of the molecular changes underlying tumor growth and progression. Recent preclinical studies have suggested that radiotherapy in combination with other targeting agents enhances the therapeutic ratio of ionizing radiation alone. However, resistance of tumor cells to chemotherapeutic drugs and radiotherapy represents a major obstacle in anti-cancer therapy. Our research aims to precisely define why some tumors fail to respond to radiotherapy in the first place, and how to interfere with this resistance pathway so that more effective treatment modalities can be developed.

Finkielstein's previous work showed that the cell cycle is arrested and cell death (apoptosis) prevented in Xenopus embryos treated with high doses of ionizing radiation at any time after the mid-blastula transition. This phenotype results from the activation of a concerted number of mechanisms that lead to cell cycle arrest at the G1/S boundary, as observed for most radiation resistant tumors as well. Thus, the Finkielstein Lab's research takes advantage of the simplicity of this model organism while using an interdisciplinary approach to identify key fundamental processes and define relevant players relevant to the response of the tumor to ionizing radiation.

The lab's initial work challenged the long-standing conventional view of radiation-induced apoptosis in which increasing exposure doses results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies.

The Finkielstein Lab's research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new paradigm, based a parallel with the photoelectric effect, that the photon energy provides the true threshold for induction of apoptosis in biological systems.

The lab explored how the energy of individual X-ray photons and exposure time, both components of the total dose, influence the occurrence of cell death in early Xenopus development. Overall, the lab's published results established that the energy of the incident photon determines the outcome of the biological system and, therefore, suggests that biological organisms display properties similar to the photoelectric effect in physical systems. These results provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes.

A fundamental feature of all living organisms is the presence of two 24h-oscillating cyclic systems. One, the circadian clock, dictates the timing of many physiological responses and provides the cell with information that can be used to anticipate daily environmental changes.

The second highly periodic system is devoted to controlling cell division and mediates the entry into and exit from the cell cycle. We now know that the proper timing of cell division is a major factor contributing to the regulation of normal growth and emerges as a fundamental process in the development of most cancers. Thus, the Finkielstein Lab investigates some of the basic mechanisms that regulate cell cycle transitions, the contribution of environmental cues to ensure timely progression throughout it, and how both cycles are interlocked at the molecular level. Accordingly, a second area of research focuses in the role of circadian clock proteins as important endogenous factors that contribute to cancer development and progression. Core circadian clock genes are defined as genes whose protein products are necessary components for the generation and regulation of circadian rhythms (from the Latin circa diem, “about a day”). Several studies have shown that about 7% of all circadian-controlled genes regulate either cell-cycle progression or apoptosis. These observations made scientists wonder whether the circadian and cell cycle systems operating within an individual cell might be interlocked by sharing some critical elements. Specifically, the Finkielstein Lab explores the means by which loss of circadian function impairs apoptosis in response to ionizing radiation, leading to genomic instability and accumulation of damaged cells. The methodologies we use are cellular and molecular biology, structure-based analysis, and systems biology.

Period 2 (Per2) is a transcriptional regulator placed at the core of the circadian clock mechanism that is responsible for generating the negative feedback loop that sustains the clock. Its relevance to human disease is underlined by alterations in its function that impacts numerous biochemical and physiological processes. When absent, it results in the development of various cancers and an increase in the cell’s susceptibility to genotoxic stress. The Finkielstein Lab's most recent findings place the circadian factor Period 2 (Per2) at the heart of the checkpoint response in cells by showing that Per2 interacts directly with the tumor suppressor p53 and its oncogenic regulator Mdm2, thereby participating in the control of downstream p53 signaling. The lab found that Per2 binds the C-terminus half of human p53 (p53) and forms a stable trimeric complex together with p53’s negative regulator Mdm2. They determined that Per2 binding to p53 prevents Mdm2 from being ubiquitinated and targeting p53 by the proteasome. Accordingly, down-regulation of Per2 expression directly impacts p53 levels whereas its overexpression influences both p53 protein stability and transcription of targeted genes. Overall, the lab's findings place Per2 directly at the heart of the p53-mediated response by ensuring that basal levels of p53 are available to precondition the cell when a rapid, p53-mediated, transcriptional response is needed. Because of the relevance of p53 in checkpoint signaling, Finkielstein and her team hypothesize that Per2 association with p53 acts as a regulatory module that influences p53’s downstream response to genotoxic stress. Unlike the trimeric complex whose distribution was confined to the nuclear compartment, Per2/p53 was identified in both cytosol and nucleus. At the transcriptional level, a reporter containing the hp21WAF1/CIP1 promoter, a target of p53, remained inactive in cells expressing a stable form of the Per2/p53 complex even when treated with ionizing radiation. Lastly, the lab established that Per2 directly acts on the p53 node, as checkpoint components upstream of p53 remained active in response to DNA-damage. Quantitative transcriptional analyses of p53 target genes demonstrated that unbound p53 was absolutely required for activation of the DNA-damage response. The lab's work provides evidence of the mode by which the circadian tumor suppressor Per2 modulates p53 signaling in response to genotoxic stress. More recently, our findings showed that Per2 and p53 rhythms were significantly out-of-phase relative to each other in cell lysates and in purified cytoplasmic fractions. These seemingly conflicting experimental data motivated the use of a combined theoretical and experimental approach focusing on the role played by Per2 in dictating the phase of p53 oscillations. Systematic modeling of all possible regulatory scenarios predicted that the observed phase relationship between Per2 and p53 could be simulated if: i) p53 was more stable in the nucleus than in the cytoplasm, ii) Per2 associates to various ubiquitinated forms of p53, and iii) Per2 mediated p53 nuclear import. These predictions were supported by a 7-fold increase in p53’s half-life in the nucleus and by in vitro binding of Per2 to the various ubiquitinated forms of p53. Lastly, p53’s nuclear shuttling was significantly favored by ectopic expression of Per2 and reduced because of Per2 downregulation. Our combined theoretical/mathematical approach reveals how novel clock regulatory nodes can be inferred from oscillating time course data.

In a third area of research, the Finkielstein Lab investigates how circadian factors sense metabolic changes and, consequently, act in cell-fate decisions. Here, a multi-technique approach, spanning from the atomic to the cellular level, will be used to elucidate the structural-functional properties of circadian transcription factors. Our objectives are to i) define crosstalk mechanisms among cell cycle, circadian and metabolic components that influence cell cycle transitions ii) study the significance of metabolic signals for circadian rhythmicity and in cell death processes, and iii) determine the structural basis for sensing metabolic changes by circadian proteins. This project will help advance various areas of research by providing a mechanistic explanation for physiological changes accompanying cell division and by elucidating more fully the interplay among cellular mechanisms.

MANIPULATION OF PLATELET AGGREGATION

Protein activators and inhibitors of blood clotting modulate platelet-mediated coagulation. Manipulating activity of these molecules is one of the major targets to control undesired effects that occur with blood clotting. Virginia Tech scientists have identified a novel protein target for intervention in thrombosis.  It is a platelet aggregation inhibitor that specifically binds and modulates the progression of platelet–mediated coagulation. Expression of this inhibitory protein is restricted to platelets, some tumor cell types, and very early stages of embryogenesis, so small molecules or other therapeutics can be tailored to intervene in a very target-specific manner.

APPLICATIONS
  • Downregulation of haemostasis in patients prone to various diseases ranging from stroke to heart disease
  • Controlling bleeding during surgery
  • Pro- or anti-thrombotic modulation to restore haemeostasis
ADVANTAGES
  • The technology targets a specific molecule released in response to platelet activation.
  • The targeted system is inherently reversible.
  • Intervention can be tightly regulated to increase or decrease thrombosis
  • Various routes of administration are possible.
TECHNOLOGY

Antithrombotic drugs often fail in the long run due to the emergence of significant compliance and safety issues, including increased bleeding.  Thus, this new technology is unique in that it targets a specific molecule that is released in response to platelet activation and otherwise remains intracellular.  Analogs can be delivered in a nanoparticle-based system to provide high stability, higher carrier capacity, selective release, and feasibility of incorporation of hydrophobic molecules. This approach will allow drug delivery by variable routes of administration, including oral and inhalation.

An important concern about antithrombotic drugs is how to reverse their effects in the event of bleeding.  The inherent reversibility of our molecule system allows the design of a counter-regulatory intervention.  Drug-based nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix, thus avoiding numerous secondary or side effects caused by accumulation of residual drug in the body. 

Click here to read a Virginia Tech article entitled "Control of blood clotting by platelets described; provides medical promise" (November 24, 2009).

For more information about this product, or to discuss licensing terms, please contact Virginia Tech Intellectual Properties, Inc. at 540-951-9374. 

LEAD INVENTORS

  • Dr. Carla V. Finkielstein is an associate professor at Virginia Tech. She is a cell and molecular biologist with a strong background in signal transduction. Finkielstein is also a trained biochemist with extensive experience in protein chemistry and biophysical techniques.
  • Dr. Daniel G.S. Capelluto is an associate professor in the biological sciences department at Virginia Tech. He has extensive experience has vast experience working with protein domains using multidimensional NMR spectroscopy. His research group indentifies binding sites at atomic resolution and executes SPR experiment.

INTEGRATED CELLULAR RESPONSES LAB UNDERGRAD RESEARCH PROGRAM

The goal of our program is to encourage students who are considering a career in science to participate in ongoing research projects and/or develop their own independent research. Our lab program provides a first-hand experience and an excellent opportunity to gain a better understanding of how biological knowledge is actually discovered. It will help students to develop the fundamental skills and techniques required to succeed in their own research while learning basic concepts in various areas of biological sciences. By working in our laboratory, students will learn what it is like to be involved in research and do science as a team.

Interested students should complete this form (MS Word) and e-mail it to Dr. Finkielstein (finkielc@vt.edu).

Requirements for Independent Study and Undergraduate Research:

  • Requirements. Applicants are expected to meet a GPA of 3.5 (or higher) and show strong enthusiasm for science. Students are encouraged to take BIOL2104, Cell and Molecular Biology, before applying.
  • Commitment. Selected undergrads are expected a minimum of 15 hours/week of laboratory work. It is most desirable that this time be available in a small number of large blocks, for example, three afternoons per week. Working on weekends is possible. It is expected students to work in the lab for more than one semester in order to complete a research project.
     

For students interested in Honors Undergraduate Research:
We have a number of research projects suitable for an honors undergraduate research thesis in cell and molecular biology. If you are considering a Honors Thesis, please send me an e-mail with a brief description of your research interests and goals, which term(s) you wish to complete your research project in, and provide an electronic copy of your resume/c.v.

High School Level Domestic Internships

High school students from Blacksburg are one step ahead of their peers around the country by joining us over the summer for their first total immersion-in lab training (In-lab-training Program). The program is intense in training and only few students are selected each summer. Students become an integral part of our laboratory shortly after they start. They spend the first couple of weeks learning basic molecular biology techniques and attending in-house lectures to help clarify basic concepts and get a better grasp of concepts. Later, each student is assigned a mentor in the lab that helps guide him/her over his/her own project. Students are invited to decide what project to join for which they are offered 3 options and need to learn how to research the literature. Students summarize their work in an oral presentation to all lab members at the end of their internship.

Previous Trainees:

2018 Sophia Sobrado, Blacksburg High School
2017 Rebecca Button, Commonwealth Governor’s School
2017 Florencia Cordova, Blacksburg High School
2017 Sofia Enriquez, Read Mountain Middle School
2017 Heeju Lim, Blacksburg Middle School
2016 Rebecca Button, Commonwealth Governor’s School
2015 William Abel, from Blacksburg High School 
2014 Elissa Fink, Southwest Virginia Governor’s school
2013 Meredith Dove, from Blacksburg High School
2013 William Abel, from Blacksburg High School
2012 Kristy Choi, from Blacksburg High School
2012 Edwin Lu, from Blacksburg High School currently at the Bio-Medical Engineering Program at University of Virginia.

GRADUATE STUDENT RESEARCH POSITION IN CELL AND MOLECULAR BIOLOGY

Two (M.Sc. or Ph.D) positions are available for highly motivated and team player graduate students. They would be responsible for leading efforts to expand our knowledge in the regulation of cell cycle transitions in early Xenopus embryo development and in understanding cell and circadian cycles cross-talk mechanisms. These projects would especially be of interest to students who want to combine multidisciplinary approaches to tackle problems in the cell biology area. Research will be conducted in a very supportive environment that includes, if required, potential collaborations.

  • Requirements. The successful applicants will have completed, by spring 2010, a B.Sc. in a biological science area (molecular biology, biochemistry, genetics, cell biology) and meet the requirements of the Virginia Tech graduate program. Previous laboratory experience (summer or honors research project) in molecular biology would be an asset. If you are interested, please forward the following information to me: a copy of your resume/c.v, a copy of a recent transcript, start date(s) you would prefer, and contact information for three references, to the address listed above. International applicants are acceptable but he/she should meet the departmental requirements. A graduate Research Assistantship is available.
  •  

POST-DOCTORAL RESEARCH POSITION IN CELL AND MOLECULAR BIOLOGY

A two-three years postdoctoral fellow position is available immediately to conduct research in the area of signal transduction of circadian transcription factors and their implication in cell cycle regulation.

  • Requirements. Applicants must have an MD and/or Ph.D. in biochemistry, molecular and/or cellular biology. The following key competencies are desired: highly motivated and interested in exploring new areas of research; good interpersonal, verbal and written communication skills. A strong background and extensive experience in cell and molecular biology techniques are essential. The candidate will receive training and/or will be exposed to a variety of specific research techniques in cell biology (eggs fertilization, tissue culture, transfections, immunohistochemistry, confocal microscopy, etc.), molecular biology (promoter analysis, DNA footprinting, in situ hybridization, arrays, etc.), biochemistry (FPLC, mass spectroscopy, enzyme assays, etc.) and bioinformatics (database mining, sequence assembly, etc). To apply please send curriculum vitae, bibliography, research interest statement and career goals and the names and contact information of three references to my address (listed on top). Salary commensurate with experience.

MULTICULTURAL ACTIVITIES

  • MAOP: The Multicultural Academic Opportunities Program: The Multicultural Academic Opportunities Program (MAOP) is an academic success community founded upon the principles of self-help, mentoring, and peer support. Central to the goal of MAOP is the promotion of diversification in the student body at Virginia Tech and on the post graduate level - particularly in the science, math, and technology areas. Through a partnership with various departments at Virginia Tech, other college and university peers, governmental, private, and non-profit institutions MAOP participants are supported with academic guidance and financial support.
  • VT-PREP: A mentored research/ classroom program sponsored by the National Institute of Health to increase diversity in the fields of biomedical and behavioral sciences.

SERVICE TO OUR COMMUNITY

Did you know that every three minutes, another woman in the United States is diagnosed with breast cancer? Every three minutes. Because our team cannot ignore this shocking statistic, we’ve made a commitment to work toward changing it, and we need your help. On October 24-25, 2009, we'll spend the weekend walking, along with thousands of other people, in the Avon Walk for Breast Cancer. We will walk at least the distance of a marathon (26.2 miles), and we may choose to walk as far as a marathon and a half. We will also raise at least $10,800 in donations to the cause. We'll have to spend the next few months training, fundraising, and preparing for the event. It's the biggest challenge we've ever taken on, but we'm very excited about doing it because we know it will make a real difference to the millions of people affected by breast cancer. The money raised is managed and disbursed by the Avon Foundation, a 501(c)(3) public charity with a mission to fund access to care and finding a cure for breast cancer. The Avon Foundation funds both local and national organizations in five key areas: medical research; education and early detection programs; clinical care; and support services, all with a focus on the medically underserved. Please help to support our efforts and this critically important cause by making a generous contribution. You can make your donation online by simply clicking on the link at the bottom of this message, which will bring you right to our team page (Researchers for the Cure). Please remember as you're making your donation that in less than the time it took to read this e-mail, another woman in the U.S. was diagnosed with breast cancer. You can also help me by passing this message along to others who may be interested in being a part of the Avon Walk for Breast Cancer. To directly donate to our Team (Researchers for the Cure) through our team leader please click here. Thanks to breast cancer survivors Meg Shrader from Augusta Health and Vernal Branch from the Virginia Breast Cancer Foundation and Constituency Coordinator for visiting our laboratory and sharing their stories with all of us. It was a fantastic opportunity to meet them and learn more on how our research benefit people. Thanks for coming! Watch Humanizing the Science of Cancer Research from The Campaign for Virginia Tech on VimeoClick here to read the full story!

As the world economic base shifts increasingly towards technology, student participation and achievement in science is becoming increasingly important. Students need to understand that early involvement in science can open gates into all domains of academia and employment. In turn, professors must provide quality education to prepare their students to live and work in a world transformed by technological growth, international competitiveness, economic globalization, and increasing demographic shifts. This research initiative focuses on recruiting and training high school students and college undergraduates through research internships, which will provide them one-on-one, intensive experiences. These laboratory internships will permit students to develop an understanding of science concepts and skills and will produce deeper, more personal relationships with practicing scientists who can serve as role models and mentors.

Through this project, efforts will focus on recruiting K-12 students from rural and urban areas in southwest Virginia while fostering undergraduate education. A second, and equally ambitious, goal of this initiative is to help resolve the scientific needs and technological challenges of our society and those in developing countries, specifically in Latin America. Here, the program focuses on two areas: K-12 education and graduate level training. In general, Latin American students are encouraged to enroll in short technical programs oriented towards the labor market. This propensity is partially explained by budget cuts in the public sector that resulted in restructuring scientific policies and increasing pressure on students to acquire more practical knowledge that will directly affect their occupational prospects. This approach, although needed in the short-term, compromises the competitiveness of each country’s future scientific program and leaves students and junior researchers unprepared to meet the needs of an evolving society and the demands of emerging technologies. The proposed research initiative aims to fulfill this gap by teaching and training high school and graduate students from both Virginia and Latin America in advanced technologies in molecular biology while fostering social interaction and promoting collaborations with international institutions.

High School International Internship Exchange Program Virginia-US / Argentina (Otto Krause Students Majoring in Chemistry)

Each year Dr. Finkielstein’s laboratory, Virginia Tech, U.S.A. and the Department of Chemistry, E.N.E.T N°1 “Otto Krause” (http://www.ottokrause.edu.ar/), Buenos Aires, Argentina solicit applications from senior chemistry majors who are interested in pursuing a career in the area of cellular and molecular biology. The Escuela Tecnica “Otto Krause” is one of the elite public high schools in Buenos Aires, Argentina. Upon completion of its six-year program, students are granted a degree in Chemical Science Technology. Most of these students continue their education in the areas of engineering, natural sciences, and biotechnology and are among the most competitive applicants in all major universities and best professionals in the country. As part of our international program, two high school students from "Otto Krause" (see list of awardees below) visited our laboratory and participated in the SIP Initiative. Both students learned basic molecular biology techniques (cloning, expression, and purification techniques for recombinant proteins as well as the basics of protein-protein interaction assays), biochemical assays (fluorescence anisotropy) and cell biology (microscopy and microinjection) approaches to investigate signaling pathways. Emilio and Matias combined their work at the lab with a number of socio-cultural activities on campus and surrounded areas. Both students had returned and enrolled in college at the School of Natural Sciences - University of Buenos Aires. Matias chose Biochemistry as a major.

Eligibility
  • Applicants must be full-time students at the E.N.E.T. N°1 “Otto Krause” at the time the application is submitted.
  • Students must be 18 or older at the time of travel.
  • The host laboratory, on a space available basis, determines placement acceptance.
  • Students are expected to write/read/speak fluent English.
How to Apply

Candidate students interested in applying should download and complete the application form (PDF) and provide Prof. S. Palomino with contact information no later than mid-September. Credential review takes place mid-November and selected students (typically two) are notified early December.

2013 Tenico Quimico Paula Borovik
2020 Tecnico Quimico Santiago Franco, Otto Krause, Argentina
2017 Student Serena Nataliccio, Colegio Nacional Buenos Aires, Argentina 
2017 Student Zoe Levy, Ben-Gurion University, Israel
2016 Ignacio Aiello, Universidad Nacional de Quilmes, Argentina
2015 Maria Mercau, Universidad de Buenos Aires, Argentina
2013 Tenico Quimico Paula Borovik (pfbok@hotmail.com)
2012 Student Nicolas Gort (nicholasgort@gmail.com )
2012 Tenico Quimico Leandro Luis Missoni (leomissoni@hotmail.com)
2012 Tenico Quimico Maximiliano Nelson Inafuku (maxi-46@hotmail.com )
2011 Tecnico Quimico David Enriquez (davide_ok@hotmail.com)
2009 - 2010 Tecnico Quimico Matias Lanus Elizalde (lanusmatias@hotmail.com)
2009 - 2010 Tecnico Quimico Emilio Santillan (tuti_globo@hotmail.com)
2008 Tecnico Quimico Victoria Tripoli (vicky_0491@hotmail.com)
2007 Tecnico Quimico Roxana Steinman (roxana_steinman@hotmail.com)
2006 Tecnico Quimico Hugo Amedei (hugo_agno3@hotmail.com)
2006 Tecnico Quimico Javier Huertas Bustos (hbjavier@gmail.com)

National Cancer Institute (U.S. National Institutes of Health) Site
General:
http://www.cancer.gov/cancertopics/types/breast (English)
http://www.cancer.gov/espanol/tipos/seno (Spanish)

What you need to know about breast cancer (English)
http://www.cancer.gov/cancertopics/wyntk/breast (PDF)
   
Lo que usted necesita saber sobre el cancer de seno (Spanish)
http://www.cancer.gov/espanol/tipos/necesita-saber/seno (PDF)

Treatment: (English)
http://www.cancer.gov/cancertopics/treatment/breast

Clinical Trials: (English)
http://www.cancer.gov/clinicaltrials/finding/treatment-trial-guide
http://www.cancer.gov/clinicaltrials/results/breast
http://www.cancer.gov/search/ResultsClinicalTrials.aspx?
protocolsearchid=6911558&vers=1

http://www.cancer.gov/newscenter/pressreleases/ALTTO
http://www.cancer.gov/clinicaltrials/finding/breast-cancer-trials-org
http://www.cancer.gov/clinicaltrials/digestpage/TAILORx

Prevention, Genetics, Causes: (English)
http://www.cancer.gov/cancertopics/prevention-genetics-causes/breast

Screening and Testing: (English)
http://www.cancer.gov/cancertopics/screening/breast(English)

Cancer Literature: (English)
http://www.cancer.gov/search/searchcancertopics.aspx?
listid=4963a5be-238c-4d3c-905d-b6b70f6a86fe

http://www.cancer.gov/search/searchcancertopics.aspx?
listid=0a86d345-b2c4-4eac-b459-28ee9f5a7ee1

http://www.cancer.gov/search/pubmed

Research and Related Information: (English)
http://fundedresearch.cancer.gov/
http://spores.nci.nih.gov/current/breast/index.htm
http://women.cancer.gov/research/breast.shtml
http://www.cancer.gov/cancertopics/ere

Statistics: (English)
http://seer.cancer.gov/statfacts/html/breast.html
http://www.cancer.gov/aboutnci/servingpeople/breast-snapshot.pdf
http://www.cancer.gov/cancertopics/factsheet/Detection/probability-breast-cancer
http://www.cancer.gov/statistics/finding
http://www.cancer.gov/statistics/understanding

Support and Advocacy Organizations (thanks to the many existing links within the ACS and AACR sites)

American Cancer Society
http://www.cancer.org/docroot/PAR/Content/
PAR_2_3_Breast_Cancer_Resources.asp

The American Cancer Society combines an unyielding passion with nearly a century of experience to save lives and end suffering from cancer. As a global grassroots force of more than three million volunteers, we fight for every birthday threatened by every cancer in every community. We save lives by helping people stay well by preventing cancer or detecting it early helping people get well by being there for them during and after a cancer diagnosis by finding cures through investment in groundbreaking discovery and by fighting back by rallying lawmakers to pass laws to defeat cancer and by rallying communities worldwide to join the fight. Get involved: http://www.cancer.org/docroot/emp/emp_2_volunteers.asp

African American Women in Touch
http://www.qualityoflife.org/services/cancer/aawit.cfm
1-574-647-1000
Memorial Hospital & Health System, 615 North Michigan St., South Bend, IN 46601
African American Women in Touch operates out of the Memorial Hospital & Health System in South Bend, Ind. The organization educates African-American women about breast cancer, provides information on early detection, and offers free mammograms to women who cannot afford them. It also provides a network of support through its monthly support meetings and annual health care symposium. African American Women in Touch provides transportation to treatment, wigs and free prostheses to women facing breast cancer.

Avon Foundation
(http://walk.avonfoundation.org/site/PageServer?pagename=walk_homepage)
The money we raise will provide women and men the breast cancer screening, support and treatment they need regardless of their ability to pay, and so that leading-edge research teams across the country can be powered by the funds they need to fuel their quest for a cure - all because of you! Are you In It To End It? Take the first step today. Get involved:
http://walk.avonfoundation.org/site/PageServer?pagename=walk_volunteer

Black Women’s Health Imperative
http://www.blackwomenshealth.org
1-202-548-4000
1420 K St., N.W., Suite 1000, Washington, DC 20005
The Black Women's Health Imperative is a health education, research, advocacy and leadership-development institution. Its website provides information, educational materials, news and other resources related to cancer and other health issues facing black women.

Breast Cancer Action
http://www.bcaction.org
1-877-2STOPBC (1-877-278-6722)
55 New Montgomery St., Suite 323, San Francisco, CA 94105
Breast Cancer Action (BCA) is a grassroots organization of breast cancer survivors and their supporters that educates people about breast cancer issues. The group's website has downloadable flyers and fact sheets on breast cancer issues. BCA also provides a booklet for newly diagnosed breast cancer patients.

The Breast Cancer Fund
http://www.breastcancerfund.org
1-866-760-8223
1388 Sutter St., Suite 400, San Francisco, CA 94109
The Breast Cancer Fund works to identify environmental and other preventable contributors to breast cancer and it advocates for their elimination. The fund, which also educates the public about cancer prevention, produces a monthly e-newsletter and fact sheets, which are all available on its website.

Breast Cancer Network of Strength
http://www.networkofstrength.org
1-800-221-2141 (English) 1-800-986-9505 (Spanish)
135 South LaSalle St., Suite 2000Chicago, IL 60607-3908
Breast Cancer Network of Strength (previously known as Y-ME National Breast Cancer Organization) provides culturally sensitive breast cancer services and resources for individuals who would like to know more about the disease. The organization’s website hosts breast cancer message boards on which participants can discuss a wide variety of topics, such as survivorship issues or advice for newly diagnosed patients. The group offers a 24-hour breast cancer hotline with interpreters in 150 languages. Callers to the hotline are matched to a survivor, patient or supporter who has had a similar experience with breast cancer. Breast Cancer Network of Strength has affiliate chapters throughout the country. It also operates a wig and breast prosthesis bank.

The Breast Cancer Research Foundation
http://www.bcrfcure.org
1-866-FIND A CURE (1-866-346-3228)
60 East 56th St., Eighth Floor New York, NY 10022
The Breast Cancer Research Foundation is dedicated to preventing and curing breast cancer by raising funds for innovative research and increasing awareness of good breast health. The foundation has a monthly e-mail newsletter and hosts an annual conference.

CancerCare
http://www.cancercare.org
1-800-813-HOPE (1-800-813-4673)
275 Seventh Ave.New York, NY 10001
CancerCare provides counseling, online and telephone support, educational information and financial assistance to patients, families and caregivers who are dealing with all types of cancer. The organization offers specialized programs that focus on the unique needs of caregivers, children and young adults, patients with rare or advanced cancers, and individuals facing end-of-life issues. CancerCare’s services are available in English and Spanish. Programs are provided by trained oncology social workers and are completely free of charge.

Cancer Hope Network
http://www.cancerhopenetwork.org
1-877-HOPENET (1-877-467-3638)
2 North Road, Suite AChester, NJ 07930
The Cancer Hope Network provides free and confidential one-on-one support to cancer patients and their families. All of its support volunteers are specially trained cancer survivors.

Cancer Really Sucks
http://www.cancerreallysucks.org
1-319-393-9681
P.O. Box 11264, Cedar Rapids, IA 52410-1264
Cancer Really Sucks is designed to help teenagers who have a loved one with cancer. The website hosts forums and monthly chat rooms in which teens can connect with other teens to discuss cancer-related issues. The website also offers advice from mental health professionals and social workers about how to cope with a loved one's cancer.

Cancer Wellness Center
http://www.cancerwellness.org
1-866-292-9355
215 Revere Drive, Northbrook, IL 60062
The Cancer Wellness Center provides support groups for people living with cancer in and around Northbrook, Ill., as well as individual support services and services for couples and families. The center also hosts a variety of stress-reducing workshops including Qigong, meditation and yoga classes, and spirituality discussion groups.

The Center for Patient Partnerships
http://www.law.wisc.edu/patientadvocacy
1-608-265-6267
975 Bascom Mall, Suite 4311, Madison, WI 53706
The Center for Patient Partnerships is an advocacy and education program that advocates for the needs and rights of people facing life-threatening diseases, including cancer, all around the world. The Center for Patient Partnerships helps patients understand their diagnoses and treatment options, deal with illness-related work issues, and handle insurance issues.

Facing Our Risk of Cancer Empowered
http://www.facingourrisk.org
1-866-288-RISK (1-866-288-7475)
16057 Tampa Palms Blvd. West PMB #373 Tampa, FL 33647
Facing Our Risk of Cancer Empowered (FORCE) provides information for women who have a high risk of developing breast or ovarian cancer. The organization offers information about hereditary cancers, risk management, and the medical and lifestyle options that are available to high-risk women. FORCE has a toll-free helpline, a message board and a chat room through which women can discuss issues that face high-risk individuals.

Family Caregiver Alliance
http://www.caregiver.org
1-800-445-8106
180 Montgomery St., Suite 1100, San Francisco, CA 94104
The Family Caregiver Alliance (FCA), which provides information and support to caregivers, publishes factsheets about caregiving issues in English, Spanish and Chinese. The organization also offers advice about how to handle caregiving responsibilities and the health impacts that stress can have on caregivers, and it also provides online support groups.

Friends of Cancer Research
http://www.focr.org
1-703-302-1503
2231 Crystal Dr. Suite #200, Arlington, VA 22202
Friends of Cancer Research is a nonprofit organization that aims to accelerate progress toward better tools for the prevention, detection and treatment of cancers. The organization raises awareness about cancer and educates the public about cancer research. It also publishes a monthly newsletter.

Gilda's Club Worldwide
http://www.gildasclub.org
1-888-GILDA-4-U (1-888-445-3248)
Gilda's Club Worldwide, 322 Eighth Ave., Suite 1402, New York, NY 10001
Gilda's Club Worldwide is a national organization with affiliate branches in cities across the country. Gilda's Club provides lectures, workshops and support groups for men, women and children whose lives have been touched by cancer. Gilda's Club also has a specially designed program, called Noogieland, for children dealing with cancer.

Gynecologic Cancer Foundation
http://www.thegcf.org
1-800-444-4441
230 West Monroe, Suite 2528, Chicago, IL 60606
The Gynecologic Cancer Foundation (GCF) is a national organization that works to ensure public awareness of gynecologic cancer prevention, early diagnosis and proper treatment. The foundation publishes brochures and educational materials about gynecologic cancer. The GCF also supports research and training related to gynecologic cancers. The foundation’s Women’s Cancer Network offers information about risk assessment and clinical trials and has a database of doctors who treat gynecologic cancers. The GCF also offers courses and telephone educational workshops for survivors of a variety of gynecologic cancers.

Inflammatory Breast Cancer Research Foundation
http://www.ibcresearch.org
1-877-STOP-IBC (1-877-786-7422)
The Inflammatory Breast Cancer Research Foundation educates people about inflammatory breast cancer (IBC). Its website offers e-mail discussion lists and other educational materials. The organization also raises funds for inflammatory breast cancer research and collects tumor samples for its IBC BioBank. The website of the Inflammatory Breast Cancer Research Foundation offers e-mail discussion lists and other educational materials.

Intercultural Cancer Council
http://iccnetwork.org
1-713-798-4617
Baylor College of Medicine, Suite 1025, 1709 Dryden St., Suite 1025, Houston, TX 77030
The Intercultural Cancer Council (ICC) is an advocacy group devoted to promoting policies, programs, partnerships and research aimed at eliminating the unequal burden of cancer on racial and ethnic minorities and medically underserved populations in the United States and its territories. It provides cancer fact sheets on its website and sponsors a biennial symposium to promote discussions of cancer in minorities and medically underserved communities.

Linda Creed Breast Cancer Foundation
http://www.lindacreed.org
1-877-99-CREED (1-877-992-7333)
260 South Broad Street, 18th Floor, Philadelphia, PA 19102
The Linda Creed Breast Cancer Foundation offers financial assistance to women in the Philadelphia region who are undergoing breast cancer treatment. The foundation provides free and low-cost mammograms to uninsured and under-insured women. The Linda Creed Breast Cancer Foundation also offers women and their families informational materials and access to cancer detection and treatment resources.The organization’s Rainbow Circle addresses the needs of lesbian, bisexual and transgender breast cancer survivors. The Linda Creed Breast Cancer Foundation also runs Safe Circle, a program for African-American women.

Living Beyond Breast Cancer
http://www.lbbc.org
1-888-753-5222
354 West Lancaster Ave., Suite 224, Haverford, PA 19041
Living Beyond Breast Cancer offers educational programs and services to women and families affected by breast cancer. Its programs include a toll-free Survivors' Helpline (1-888-753-5222), a free quarterly newsletter, publications for African-American and Latina women, and networking programs for young survivors and women of color.

Malecare
http://www.malecare.com
1-212-673-4920
125 Second Ave., Room 13, New York, NY 10003
Malecare is an organization devoted to the health needs of men. The organization provides information on prostate cancer, testicular cancer and male breast cancer. Malecare also provides information on the sexual side effects of cancer treatment. It also hosts support groups throughout the nation. The organization facilitates cancer support groups for gay men and also reaches out to lesbian, gay, bisexual and transgender (LGBT) people through its LGBT cancer project. Information on the Malecare website is available in a variety of languages, including Spanish, French, Italian and Russian.

Mautner Project, the National Lesbian Health Organization
http://www.mautnerproject.org
1-202-332-5536
1707 L St., N.W., Suite 230, Washington, DC 20036
The Mautner Project is a support and advocacy organization dedicated to improving the health of lesbians and their families, especially those with cancer and other life-threatening diseases. The Mautner Project aims to educate lesbians about their health and to educate health care providers about their lesbian patients. Among its many activities, the Mautner Project coordinates in-person support groups and offers phone support services.

Mothers and Daughters
http://www.mothersdaughters.org
1-410-778-1982
Mothers and Daughters is an organization for the mothers of breast cancer patients and survivors. The organization provides support for mothers and matches them with other women who have daughters with breast cancer. Mothers and Daughters also provides support for women diagnosed with the disease. The group publishes informational booklets for mothers and for women who are diagnosed with breast cancer.

National Asian Women’s Health Organization
http://www.nawho.org
1-925-468-4120
4900 Hopyard Road, Suite 100, Pleasanton, CA 94588
The National Asian Women’s Health Organization (NAWHO) aims to raise awareness about the health needs of Asian-American women. The organization’s mission covers a wide range of health issues including breast and cervical cancer. NAWHO began the Asian American Women’s Breast and Cervical Cancer Project in 1995 as a way to address the needs of Asian-American women living with breast and cervical cancers.

National Breast Cancer Coalition
http://www.natlbcc.org
1-800-622-2838
1101 17th St., N.W., Suite 1300, Washington, DC 20036
The National Breast Cancer Coalition (NBCC) aims to eradicate breast cancer by focusing government, research institutions and consumer advocates on breast cancer. The coalition informs, trains and directs patients and others in effective advocacy efforts. The NBCC's goals include promoting breast cancer research improving access to high-quality breast cancer screening, diagnosis, treatment and care and increasing the involvement and influence of breast cancer survivors and activists in the decision-making processes that impact the disease. The NBCC website provides a list of fact sheets, analyses and position papers related to breast cancer.

National Lung Cancer Partnership
http://www.nationallungcancerpartnership.org
1-608-233-7905
222 North Midvale Blvd., Suite 6, Madison, WI 53705
The National Lung Cancer Partnership works to increase awareness about lung cancer and raise funds for treatment. The organization provides information for lung cancer patients and maintains a calendar of lung cancer events across the country.

Nueva Vida Inc.
http://www.nueva-vida.org
1-202-223-9100
2000 P St., N.W., Suite 620, Washington, DC 20036
Nueva Vida is made up of Latina breast cancer survivors and Latino health care professionals who are committed to providing culturally sensitive support services for Latinas living with cancer in the Washington metropolitan area. Nueva Vida offers support, education and resources in both Spanish and English.

Pennsylvania Breast Cancer Coalition
http://www.pabreastcancer.org
1-800-377-8828
Trout Run Business Center, 344 North Reading Road Ephrata, PA 17522
The Pennsylvania Breast Cancer Coalition provides support to women in Pennsylvania who are impacted by breast cancer. The organization hosts an annual conference and offers patients the opportunity to interact with other survivors as well as medical professionals and patient advocates. The coalition operates support groups throughout the state.

Research Advocacy Network
http://www.researchadvocacy.org
1-877-276-2187
309 E. Rand Road, Suite 175, Arlington Heights, IL 60004
The Research Advocacy Network (RAN) focuses on education, support and connecting patient advocates with the research community to improve patient care. It develops materials to advance patient-focused research and works to equip advocates for more effective advocacy. The organization hopes to collapse the amount of time it takes for research results to reach community practice.

SHARE: Self-Help for Women With Breast or Ovarian Cancer
http://www.sharecancersupport.org
1-866-891-2392
1501 Broadway, Suite 704A, New York, NY 10036
SHARE offers support to women with breast or ovarian cancer in the New York metropolitan area. Cancer survivors lead SHARE's support groups and staff its hotlines. There are separate hotlines for breast, ovarian and Latina patients programs for families and friends affected by breast and ovarian cancer and a variety of support groups and other programs. SHARE offers educational programs on topics such as lymphedema, clinical trials, bone health, hormonal treatments, access to medical care and advocacy.

Sharsheret
http://www.sharsheret.org
1-866-474-2774
1086 Teaneck Road, Suite 3A, Teaneck, NJ 07666
Sharsheret is a national organization of cancer survivors that provides culturally sensitive support and information to Jewish women facing breast cancer. Sharsheret also offers specialized information for the friends and families of breast cancer patients and for women who have a high risk of developing the disease.

Sisters Network Inc.
http://www.sistersnetworkinc.org
1-713-781-0255
2922 Rosedale St., Houston, TX, 77004
Sisters Network increases awareness about the impact of breast cancer on the African-American community. The organization provides African-American women with educational materials about breast cancer risk, symptoms and treatment. Sisters Network maintains support-group chapters in about three dozen states.

Susan G. Komen for the Cure
http://www.komen.org
1-877-GO KOMEN (1-877-465-6636)
5005 LBJ Freeway, Suite 250, Dallas, TX 75244
Susan G. Komen for the Cure (previously known as the Susan G. Komen Breast Cancer Foundation) funds research grants and supports breast cancer education, screening and treatment projects in communities around the world through an extensive network of United States and international affiliates. The organization also provides information about breast health and breast cancer, treatment options and community support groups through a national toll-free helpline (1-877-GO KOMEN or 1-877-465-6636) and distributes a variety of educational materials to those affected by breast cancer. Helpline support is available in Spanish.

Virginia Breast Cancer Foundation
http://www.vbcf.org
1-800-345-VBCF (1-800-345-8223) (toll free)
5004 Monument Avenue, Suite 102, Richmond, VA 23230
The Virginia Breast Cancer Foundation (VBCF) is a grassroots organization committed to the eradication of breast cancer through education and advocacy. The VBCF holds support group meetings and maintains a calendar of breast cancer events in Virginia. It also provides a packet of information for newly diagnosed women.

The Wellness Community
http://www.thewellnesscommunity.org
1-888-793-WELL (1-888-793-9355)
919 18th St., N.W., Suite 54, Washington, DC 20006
The Wellness Community is a nationwide organization with more than two dozen local chapters. It provides online support groups in English and Spanish and has an online resource guide with information about various types of cancer, clinical trials, and advice on managing treatment side effects.

Young Survival Coalition
http://www.youngsurvival.org
1-877-YSC-1011 (1-877-972-1011)
61 Broadway, Suite 2235, New York, NY 10006
The Young Survival Coalition (YSC) is dedicated to the concerns and issues that are unique to young women and breast cancer. The YSC has an online bulletin board that young survivors can use to communicate with one another and it publishes informational brochures and a quarterly newsletter. The organization also has affiliate branches that host meetings around the country. In addition to educational and support services for survivors, the YSC works to educate community and government officials about the reality of breast cancer diagnosis in young women.

Center for Circadian Biology (BioClock Studio)
https://ccb.ucsd.edu/the-bioclock-studio/education-resources/index.html

Society for Research in Biological Rhythms
https://srbr.org/

Circadian Rhythms - National Institute of General Medical Sciences (NIGMS)
https://www.nigms.nih.gov/education/pages/factsheet_circadianrhythms.aspx

BioClock @ the University of Notre Dame
https://www3.nd.edu/~bioclock/

Circadian Rhythms – The Jackson (Jax) Laboratory (mouse models)
https://www.jax.org/research-and-faculty/research-centers/systems-neurogenetics/projects/circadian-rhythm

CGDB: a database of circadian genes in eukaryotes
Nucleic Acids Research, 2016; 10.1093/nar/gkw1028
http://cgdb.biocuckoo.org/

CirGRDB: a database for the genome-wide deciphering circadian genes and regulators 
Nucleic Acids Research, 2018;
https://doi.org/10.1093/nar/gkx944
http://cirgrdb.biols.ac.cn/

CYCLOPS
PNAS, 2017,114 (20) 5312-5317; 24,2017
https://doi.org/10.1073/pnas.1619320114

CircadiOmics: circadian omic web portal
Nucleic Acids Research, 2018,
https://doi.org/10.1093/nar/gky441

Proteomics Tools
http://ca.expasy.org
http://tools.neb.com/NEBcutter2.index.php

Protocols
General Molecular Biology
http://molbiol.ru/eng/protocol
http://omrf.urhsc.edu/~frank/toc.html
http://www.ebioinfogen.com/phagef.htm

PCR-related Protocols
http://www.ebioinfogen.com/pcrf.htm

Microarray Protocols
http://www.ebioinfogen.com/microarray.htm

Plasmid-Related Protocols
http://www.ebioinfogen.com/plas_mid.htm

Databases
Protein
http://www.rcsb.org/pdb/home/home.do

Gene Expression
http://www.ncbi.nim.nih.gov/projects/geo

Gene Regulation
http://www.gene-regulation.com/pub/databases.html
http://www.cbil.upenn.edu/cgi-bin/tess/tess
http://www.genomatix.de/online_help/help_eldorado/introcution.html

Entrez
http://www.ncbi.nim.nih.gov/Database

Online Mendelian Inheritance in Man
http://www.ncbi.nim.nih.gov/entrez/query.fcgi?db=OMIM

Analysis of Phosphorylation Sites
http://bioinformatics.lcd-ustc.org/PPSP
http://973-proteinweb.ustc.edu.cn/gps/gps_web/links.php
http://phospho.elm.eu.org/links.html

Bookshelf (Online access to textbooks)
http://www.ncbi.nim.hih.gov/entrez/query.fcgi?db=Books

Annual Impact Factor 2002-2004
http://www.cncis.ro/PDF/IF_2004.pdf

DNA Sequencing Core Virginia Tech (password required)
https://lims.vbi.vt.edu:8443/graphlogic/index.do

Xenopus Links
http://www.xlaevis.com/ A fine site with a quick overview of useful info on handling, housing, husbandry, etc.
http://www.xenopus.com/husbandry.htm Loads of info on care of adult Xenopus.
http://www.enasco.com/prod/Static?page=xenopus We buy our frogs exclusively from Nasco
http://genome.jgi-psf.org/Xentr3/Xentr3.home.html A full-service site for X. tropicalis info.
http://www.sanger.ac.uk/cgi-bin/blast/submitblast/x_tropicalis Blast for Xenopus ESTs.
http://xenopus.nibb.ac.jp/ The web-catalog for the NIBB Xenopus EST database, now includes an in situ pattern browser.
http://www.xenbase.org/ The full-service Xenopus Community website.
http://worms.zoology.wisc.edu/frogs/mainmenu.html Really cool amphibian embryology tutorial.

If you are interested in how water quality in your Xenopus colony affects the eggs you get, please read:
Green, S.L. Factors affecting oogenesis in the South African clawed frog (Xenopus laevis)Comp. Med. 2002, Aug; 52(4): 307-12.

Godfrey, E.W., Sanders, G.E. Effect of water hardness on oocyte quality and embryo development in the African clawed frog (Xenopus laevis). Comp. Med. 2004, Apr; 54(2): 170-5.