OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)

EDUCATION/TRAINING:

A. Personal Statement

I have the expertise, training and motivation necessary to successfully carry out the proposed research project. 
During my postgraduate scientific formation in the field, started in 2009 in my Ph.D, I got a broad background by working with breast cancer patients, especially to understand the main clinicopathological features associated with disease poor prognosis, working at Londrina State University – Londrina Cancer Hospital and the National Cancer Institute. I have worked most of this time with Dr Rubens Cecchini. Dr Luciana Pizzatti and Dr Eliana Abdelhay team, and together we have mapped more than 5,000 patients from different regions of Brazil, showing distinct disease profiles and epidemiological risks. As PI or co-Investigator on several Brazilian university- and government-funded grants (CNPq, Araucaria Foundation, Ministry of Health, Serrapilheira Institute), I laid the groundwork for the proposed research by understanding the biological mechanisms related with disease behavior, as disease spreading, molecular subtyping, immune response profiles and clinical issues as response to chemotherapy, as documented in my list of publications.  In addition, I successfully administered the projects and collaborated in a broad scientific network. We have provided analytical support in the field of redox analyses, developed from our cancer studies, for more than 10 laboratories in Brazil, that resulted in several peer-reviewed publications from each project in the field of immunopathology of neglected diseases, autoimmunity and neurodegenerative conditions.
 Our lab is also a member of the Brazilian Reproducibility Initiative, and is enrolled in the validation of experiments concerning immunohistochemistry and western blot techniques. Moreover, I have participated of the Canadian Halifax Taskforce, a team of several scientists worldwide that were dedicated to discuss the main gaps in cancer research to reach the clinical practice and overcome treatment challenges. The result of this taskforce was published as a special issue in the prestigious journal Seminars in Cancer Biology (IF 9.66), in which I have contributed with 2 articles regarding tumor biology understanding. In the last few years, I have moved to the State University of West Paraná, located in a geographic rural area, and started a collaboration with several institutions with the aim to map and identify the role of environmental risk factors as determinants of breast cancer risk and disease prognosis in the local population. We have studied a region formed by 27 municipalities, formed by almost 600,000 inhabitants. We have built a biobank, actually composed by samples from more than 600 women that are mainly occupied in agriculture, which includes matched saliva, whole blood, normal breast tissue and breast cancer samples collected over time. In these samples, we have performed an extensive mapping of pesticide contamination, as well measured its spreading and persistence as organic pollutants in the local environment. We also have a complimentary solid database regarding the detailed clinicopathological information from these women. The current application builds logically on my prior work, and the collaborative network with several experts from Epidemiology, Geography, Oncology and Environmental Heath that strengthens our team. Recently we have started to prepare our data about pesticide exposure and breast cancer for publication, and at least 4 manuscripts are under review.

Actually we have supported the Paraná State Government to understand the role of pesticide environmental contamination as a risk factor for breast cancer development, and have collectively created a Pesticide Observatory to share this information. Due to the contribution of our team to national science, Paraná state is supporting me with a scientific productivity fellow. During 2016-2017 my career was disrupted due to maternity and family obligations, but after this it was successfully resumed.

B. Positions and Honors

Positions and Employment

1999-2011                  Fellow in Biochemistry undergraduate, master and Ph.D in Experimental Pathology, State University of Londrina, Brazil.

2011-2013                  Postdoctoral Internship, National Cancer Institute, INCA, Rio de Janeiro, Brazil

2014-present  Adjunct Professor and Researcher, State University of West Paraná, Unioeste, Brazil.
  

2014-present  Collaborating scientist, State University of Londrina, Experimental Pathology Program, Brazil.

2019- present Visiting Researcher, Harvard University, Department of Environmental Health, T.H. Chan School of Public Health, USA.

Other Experience and Professional Memberships

2013                            Consultant, Fundacion La Marató TV3, Spain.

2013                            Consultant, Agència d`Ínformació, Avaluació i Qualitat en Salut, Italy.

2013-2014                  Board of advisors, Member, National Council for Scientific and Technological Development (CNPq), Brazil.

2014-present  Board of advisors, Member, Brazilian Ministry of Health.

2015                            Board of advisors, Member, Espirito Santo Support Foundation, FAPES, Brazil.

2017                            Consultant, Cearense Foundation to Support Scientific and Technological Development, Brazil.

2017                            Consultant, Department of Science and Technology, Department of Science, Technology, Brazil.

2017-present  Board of advisors, Member, Araucária Foundation to Support Scientific and Technological Development, Paraná state, Brazil.

2019-present  Board of advisors, Member, Bank of Evaluators of the National System for the Evaluation of Higher Education in Brazil, BASis, Ministry of Education - MEC, Brazil.

Honors

2019                            Award for Best Science Education Project, Brazilian Society of Immunology, Brazil.

2019                            Honorable mention for Oral Presentation in the Paraná Medical Association Congress, Brazil.

2019                            Award for Best Poster, PUC Health Tech Medical Congress, Brazil.

2018                            Award for Best scientific initiation project in the health area, National Council for Technological Development, Brazil.

2018                            Honored Professor appointed by Medical students, State University of West Paraná, Brazil.

2017                           Award, Prevent Cancer Now - Cancer Prevention Award, Canada.

2016                           Award for Best scientific initiation project in the health area, National Council for Technological Development, Brazil.

2016                            Award, Eric Roger Wroclawski Award, Best Article of the Year, Albert Einstein Hospital, Brazil.

2015                           Honorable mention, Poster presentation, Brazilian Society of Immunology, Brazil.

2014                            Award, Best project from the Research Program for the Brazilian Healthcare System, Ministry of Health, Brazil.

2013                            Award, Ricardo Pasquini - Young Investigator, Brazilian Society of Bone Marrow Transplantation.

2012                            Honorable mention, Annual Congress of SBFis, Brazilian Society of Physiology.

2011                            Finalist doctoral thesis of the Science and Technology Incentive Award for the Brazilian Healthcare System, Ministry of Health.

2009                            Award, Best Poster, Immunorib Awards, Brazilian Society of Immunology, Brazil.

C. Contribution to Science

Early publications in breast cancer: My early publications aimed to understand the molecular redox mechanisms enrolled in breast cancer biology, as well to comprise the profile of inflammatory mediators in the context of disease prognosis. These initial papers, most produced during my Ph.D, helped to understand the picture of the systemic oxidative profile found among different clinical stages and molecular subtypes of breast cancer. Further, these papers contributed to knowledge about the toxic mechanisms induced acutely by chemotherapy and driven by oxidative stress mediators. We also demonstrated evidences that support the existence of a differential oxidative status between the normal and the cancerous breast tissue, adding information to literature in the field of tumor redox biology by also performing
in vitro studies. I served as the primary investigator or co-investigator in all of these studies.

1. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.
   Panis C et al. Breast Cancer Res Treat. 2012 Jun;133(3):881-8.

1. Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients. Herrera AC, Panis C et al. Cancer Immunol Immunother. 2012 Nov;61(11):2193-201.

c)    Immunological effects of taxol and adryamicin in breast cancer patients.
Panis C et al. Cancer Immunol Immunother. 2012 Apr;61(4):481-8.

1. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma. Panis C, Victorino VJ, Herrera AC, Cecchini AL, Simão AN, Tomita LY, Cecchini R. Oxid Med Cell Longev. 2015;2015:6429812.

Omics-based studies in breast cancer: In addition to the contributions described above, with a team of collaborators, I started to work on high-throughput strategies to profile breast cancer intrinsic proteins and genes that are related to disease aggressiveness and response to the treatment. During this period, we demonstrated for the first time that the molecular subtypes of breast cancer presented completely distinct patterns of proteins expression in both plasma and tumor samples. We also shown the existence of an intermediate molecular profile of breast cancer by using genomic and proteomic approaches, the triple negative and intracellular HER2-domain positive breast cancer. Further, our team designed proteomic screenings aiming to understand the impact of cytotoxic chemotherapy in the systemic plasmatic profile of breast cancer patients, as well we demonstrated in a recent study that this tool is valuable to identify distinct patterns of proteins associated with the development of chemoresistance.

1. Label-free proteomic analysis of breast cancer molecular subtypes.
   Panis C et al. J Proteome Res. 2014 Nov 7;13(11):4752-72.

1. The positive is inside the negative: HER2-negative tumors can express the HER2 intracellular domain and present a HER2-positive phenotype.
   Panis C et al. Cancer Lett. 2015 Feb 1;357(1):186-195.

1. Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer.
   Panis C et al. Tumour Biol. 2016 Mar;37(3):3775-83.

1. Label-Free Proteomics Revealed Oxidative Stress and Inflammation as Factors That Enhance Chemoresistance in Luminal Breast Cancer. Pires BRB, Panis C, Alves VD, Herrera ACSA, Binato R, Pizzatti L, Cecchini R, Abdelhay E. Oxid Med Cell Longev. 2019 Aug 8;2019:5357649.

Recent network: More recently, our scientific network has expanded, and we have worked together to contribute in the field with some review studies. We have reviewed the epidemiology of breast cancer in Brazil, and the main factors of our public health system that contribute to the actual picture of disease regarding diagnosis, treatment, mortality and prognosis. I have participated in the Halifax Taskforce, and initiative from Canadian scientists to discuss some treatment gaps of science that need to be improved to help patients and doctors to overcome cancer mortality. From this partnership, it was produced a Special Issue in the journal Seminars in Cancer Biology (IF 9,6), in which I co-authored 2 papers. In collaboration with our master and Ph.D students, we produced several book chapters addressing the molecular mechanism that affect breast cancer biology, most in the context of redox biology and inflammation. Recently, since our team started to work with the pesticide issue, we were invited to publish a chapter in a book dedicated to pesticide contamination issues worldwide, and we addressed the main challenges of Brazil regarding drinking water and food contamination. Other papers that refer to pesticides and breast cancer are now under review.

1. A multi-targeted approach to suppress tumor-promoting inflammation. Samadi AK et al (Panis C). Semin Cancer Biol. 2015 Dec;35 Suppl:S151-S184.

1. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Block KI et al. (Panis C). Semin Cancer Biol. 2015 Dec;35 Suppl:S276-S304.

1. Mitochondrial Dysfunction in Breast Cancer A Potential Target from the Bench to Clinical Therapeutics. Scandolara TB et al. (Panis C). In: Sajal Chakraborti; Naranjan S Dhalla; Nirmal Ganguly; Madhu Dikshit. (Org.). Oxidative Stress in Heart Diseases. Springer Nature, 2019, v. 1, p. 1.

1. Candiotto LP et al (Panis C). Regulation and Monitoring of Pesticide Residues in Water and Food in Brazil. In: Ashish Sachan; Suzane Hendrich. (Org.). Regulation And Monitoring Of Pesticide Residues In Water And Food In Brazil. 1ed.-: Apple Academics, 2017, v. 1, p. 1-50.

Other papers can be found in my complete list of publications in Pubmed:
https://www.ncbi.nlm.nih.gov/pubmed/?term=panis+c+or+panis+carolina

2.    ID. Additional Information: Research Support and/or Scholastic Performance

Ongoing Research Support

1. PI of the proposal awarded with funding from PPSUS Program – Ministry of Health, Brazil, grant 01/2016 (R$ 87,200) – Occupational exposure to pesticides and its relationship with breast cancer aggressiveness in rural women from Paraná Southwest, Brazil.
2. PI of the proposal awarded with funding from Araucária Foundation, Paraná state, Brazil, grant 09/2016 (R$ 34,000) - Molecular approach to stress in human breast cancer.
3. Collaborator with Dr. Wander Rogério Pavanelli in the proposal awarded with funding from National Council for Technology Development, Brazil, grant 14/2013 (R$ 60,000) - Natural And Synthetic Compounds As Therapeutic Alternatives For The Treatment Of Leishmaniosis.
4. Collaborator with Dr. Ivete Conchon in the proposal awarded with funding from PPSUS Program – Ministry of Health, Brazil, grant 04/2013 (R$ 120,000) - 
   Analysis Of The Immunomodulative Activity Of Concanavaline A In Experimental Leishmaniosis For Therapeutic Purposes.
   

Completed Research Support

1. PI of the proposal awarded with funding from the Superintendence of Science, Technology and Higher Education of Paraná, SETi, Brazil, grant 07/2014 (R$ 82,500) – Science at school project.
   
2. PI of the proposal awarded with funding from the National Council for Technology Development, Brazil, grant 14/2013 (R$ 28,000) - Predictive serological markers of cardiovascular risk in breast cancer chemotherapy.
   
3. Co-PI with Dr. Rubens Cecchini in the proposal awarded with funding from PPSUS Program – Ministry of Health, Brazil, grant 01/2013 (R$ 350,000) - Characterization of oxidative mechanisms involved in the development of resistance to chemotherapy in breast cancer and identification of potential markers of chemoresistance.
4. Co-PI with Dr. Vanessa Jacob Victorino in the proposal awarded with funding from Institutional Innovation Incentive Program (PROINOVA 2018-2019, R$ 14,000), Federal Institute of Rio de Janeiro - Campus Eng. Paulo de Frontin.