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Parker B. Francis Summer Fellowship Program at the University of Kansas PROGRAM INFORMATION AND APPLICATION INSTRUCTIONS

Program information, the application and recommendation forms may be downloaded at the following link: http://www.kumc.edu/school-of-medicine/internal-medicine/pulmonary-and-critical-care/undergraduate-summer-research-fellowship.html

or you may obtain the forms by emailing the PBF Program Administrator, Deborah Snapp, at [email protected].

The student will list on their application two faculty members at the University of Kansas who are conducting research with broad relevance to pulmonary diseases as potential mentors for their summer fellowship. Attached is a list of potential mentors or the applicant may identify a mentor not on this list who is a faculty member with an appropriate research program at the University of Kansas. To apply the applicant must:

1. Submit the application as a single pdf file 2. Submit an official college transcript in a sealed envelope or by email from the institution3. Submit two confidential recommendations (on the PBF Summer Fellowship Program recommendation

form). These should be submitted directly by the recommender.

IMPORTANT NOTES REGARDING COMPLETING THE APPLICATION Please carefully follow all instructions for each section of the application. Please note that the application will not be considered if it:

1. is received after the deadline, 2. is incomplete, 3. does not comply with the format or guidelines for the number of words.

AFTER COMPLETING THE PBF SUMMER FELLOWSHIP APPLICATION FORM: Check that your margins are at .5”, text is in single-line spacing, Arial 11-point font Check to be sure you have not exceeded the specified word limits for each section Convert the Word application file to a pdf file Email this single pdf application file to [email protected] Check back with the individuals writing recommendations to be sure their recommendations were

completed using the PBF Summer Fellowship recommendation form and that they are submitted prior to the deadline of Monday, February 1, 2018.

Check with your institution to be sure your college transcript has been sent.

SUBMISSION INSTRUCTIONS

APPLICATION REVIEW PROCESSApplications are reviewed by members of the Parker B. Francis Fellowship Program Council of Scientific Advisors. We will notify all applicants of the award decision no later than March 1, 2018.

QUESTIONS SHOULD BE ADDRESSED TO: Deborah Snapp, [email protected]

ALL APPLICATION MATERIALS MUST BE RECEIVED NO LATER THAN February 1, 2018. APPLICATION should be emailed as a single pdf file OFFICIAL TRANSCRIPT sent directly by the college via email or US mail TWO CONFIDENTIAL LETTERS OF RECOMMENDATION on the PBF Summer Fellowship recommendation form sent

directly by the letter writer (preferably emailed pdf file or may be sent by US mail) Submit materials to: Deborah Snapp, Administrator / PBF Summer Fellowship Program Email: [email protected] US mail: 8427 SE 35th Street / Mercer Island, WA 98040

2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS

Listed below are faculty at the University of Kansas who are potential 2017 PBF Summer Fellow Mentors. You may also request mentors not on this list who hold faculty positions and are conducting relevant research at the University of Kansas.

Shrikant Anant, PhDProfessor, Department of Molecular and Integrative PhysiologyAssociate Director for Prevention and Cancer ControlAssociate Dean for ResearchEmail: [email protected]

Dr. Anant’s research focus is on posttranscriptional gene regulation in inflammation and cancer, cancer stem cells and chemoprevention.

Research in the laboratory is focused on various aspects of cancer biology at the molecular level. Specific research areas include: (a) regulation of gene expression at the levels of mRNA stability and translation, (b) cancer stem cells, and (c) mechanisms of chemoprevention by dietary factors and its novel derivatives.

Regulation of Gene Expression: A major focus of the laboratory has been in the role of RNA binding proteins in posttranscriptional control of gene expression. Dr. Anant’s group has identified two specific RNA binding proteins, CUGBP2 and RBM3, and are currently characterizing the mechanisms by which these proteins interact with the mRNA to regulate its stability and translation. They are also determining the effect of these RNA binding proteins in induced pluripotency.

Cancer Stem Cells: Stem cell research provides a foundation for therapeutic advancement in oncology. Currently, identification and characterization of reliable stem cell markers is the top priority in this field. Dr. Anant’s research has characterized multiple markers and identified protooncogene-induced cancer stem cells (PICSCs), a unique resource to study the biology and therapeutic targeting of specific cancer-initiating cells within the tumor. Current research is determining the microRNA profiles and the signaling mechanisms that regulate their expression in these cells.

Dietary Chemoprevention and Novel Therapeutics: Another focus of the laboratory is to determine mechanisms by which progression of a normal cell to a cancer cell can be prevented. A specific interest is determining mechanisms by which dietary phytochemicals such as curcumin and marmelin regulate gene expression in colorectal, breast and pancreatic tumors. Dr. Anant’s lab has developed novel therapeutic agents based on natural dietary compounds and are testing them for efficacy against various cancer cells. Current research includes the molecular analysis of cancer cells following treatment with these agents.

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS

Nikki Cheng, PhDAssociate ProfessorDepartment of Pathology and Laboratory MedicineEmail: [email protected]

Dr. Cheng’s laboratory investigates the functions of stromal fibroblasts in the tumor microenvironment during breast cancer progression.

Fibroblasts are a major cellular component of the tumor microenvironment and influence cancer cell behavior directly and indirectly through secretion of soluble factors, including growth regulators and angiogenic factors.  While genetic alterations in breast fibroblasts may exert pro-tumorigenic effects, little is known of the cellular and molecular signals that regulate fibroblast functions in the tumor microenvironment.

Studies in Dr. Cheng’s laboratory suggest that fibroblasts may interact with breast cancer cells to regulate cancer cell motility and invasion through chemokine signaling.  Using multiple approaches, including mouse models of cancer, molecular biology, biochemistry and cell culture systems, Dr. Cheng’s research is directed at understanding the functions of stromal cells in the tumor microenvironment and the impact of the tumor microenvironment on metastatic spread.

Her research team has recently identified potentially novel roles for CXCL1 and CCL2 chemokine signaling in regulating fibroblast: epithelial interactions during lung metastasis.  Using 3D cell culture models, future studies seek to 1) characterize the role of lung fibroblasts on breast cancer cell growth, survival and invasion in the context of chemotherapy treatment, 2) examine the role of putative CCL2 and CXCL1 chemokine mechanisms in regulating fibroblast: cancer cell interactions in the lung. These studies will have important implications on the treatment of lung metastasis.  By identifying and understanding the molecular signals that create a tumor permissive environment, these studies may contribute to identifying new molecular targets for therapy and developing improved methods for diagnosing and treating metastatic breast cancer.

Jeremy Chien, PhD9/17 Page 2 of 9

2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORSAssistant ProfessorDepartment of Cancer BiologyEmail: [email protected]

The primary objectives of Dr. Chein’s research program are to understand the genetic basis of cancer and to translate this knowledge into clinical applications to improve the early detection and the treatment of cancer. To support these objectives, his current research focuses on three areas: Cancer Genomics, Functional Genomics, and Molecular Cancer Therapeutics. In particular, they are interested in characterizing the genetic alterations associated with lung cancer and malignant mesothelioma and developing rational combination of targeted therapies and immunotherapies for lung cancer and malignant mesothelioma.

Summer research fellows will conduct independent research studies focusing on how tumor stroma affect tumor cell behavior and response to anti-cancer therapies. Research will involve in vitro cell culture, cytotoxicity assays to assess

the effect of drugs on cancer cells, immunoblot analysis to define signal transduction in response to co-culture with stroma cells and drug treatments.

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS

Navneet Dhillon, PhD Associate Professor, Division of Pulmonary and Critical CareEmail: [email protected]

Dr. Dhillon’s research interests are focused on unraveling the molecular pathways involved in HIV-infection associated pulmonary disorders, particularly vasculature dysfunction associated with cardio-pulmonary complications.

In general, the prolonged survival of human immuno-deficiency virus (HIV-1)-infected patients with the use of antiretroviral therapy has resulted in increase in the incidence of non-infectious cardio-vascular and pulmonary complications such as coronary heart disease and pulmonary arterial hypertension (PAH), especially among intravenous drug users. The long term goal of the lab is to understand mechanistically how HIV-1 and drugs of abuse interact and contribute to the pulmonary vascular remodeling, which can later help in developing novel and effective therapeutic intervention strategies against cardiopulmonary complications associated with HIV-infection.

Current research is aimed at: elucidating the underlying molecular mechanism(s) involved in the

augmentation of HIV-protein related pulmonary smooth muscle hyperplasia in the presence / absence of illicit drugs;

exploring the role of extracellular vesicles released by macrophages in HIV associated pulmonary arteriopathy;

defining the mechanism(s) involved in autophagy mediated augmentation of HIV-related pulmonary endothelial dysfunction.

Dr. Dhillon’s research is currently supported by multiple grants from National Institute of Health.Students will join a post doctorate fellow or a research technician to work on one of the above mentioned projects and will get hands on experience on various molecular biology, cell-culture and basic laboratory techniques. Students will also get an opportunity to observe the catheterization and hemodynamic analysis on an animal model system.

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS

Edward Ellerbeck, MD, MPHProfessor, Chairman of the Department of Preventive Medicine and Public HealthEmail: [email protected]

Dr. Ellerbeck’s research focuses on improving primary care delivery and delivery of preventive services with a particular focus on tobacco control, cancer screening, diabetes management, and cardiovascular health.

He has experience conducting interventional and observational studies on quality of care in hospitals and primary care practices. Dr. Ellerbeck developed, implemented and tested a ‘chronic care model’ for smoking cessation, demonstrating that smokers are willing to make repeated cessation attempts over a 2-year period of follow-up. He has also conducted direct observation of smoking cessation interventions in physician offices and academic detailing among 300 Kansas primary care physician offices to improve delivery of preventive services. 

Dr. Ellerbeck is Medical Director of “U Kan Quit” at KUMC hospital.  Students would work on projects examining the delivery of smoking cessation services to hospitalized patients.

Kimber P. Richter, PhD, MPHProfessor, Preventive Medicine and Public HealthEmail: [email protected]

Dr. Richter is Director of UkanQuit at KUMed, a bedside tobacco treatment service for our hospital inpatients, which has served over 10,000 patients since its inception in 2006.

Based on UKanQuit, Dr. Richter leads an NIH-funded study to identify the best way to link hospitalized smokers with treatment after discharge.  She was also principal investigator of Connect2Quit, an NIH-funded trial on the effectiveness of real-time internet video counseling for smoking cessation for rural smokers in Kansas.  Her team is currently analyzing data on a national survey conducted among substance abuse treatment facilities to identify what they do (and don’t do) to help their clients quit smoking. 

Dr. Richter is President of the Association for Medical Education and Research on Substance Abuse and is on the editorial board for the new peer-reviewed journal Addiction Science and Clinical Practice.

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS

Tomoo Iwakuma, MD, PhDAssociate ProfessorDepartment of Cancer BiologyEmail: [email protected]

Dr. Iwakuma's laboratory conducts cancer research, specifically cancer progression in bone and soft tissue sarcoma and other types of carcinoma.

Over 50% of human cancer has mutations in the tumor suppressor p53 which regulates cell cycle progression, cell death, senescence, chromosome integrity, DNA repair, and metastasis. Mutations in the p53 genes are especially high in lung cancers and contribute to aggressive behaviors of lung cancers through their oncogenic gain-of-function activities. Increasing evidence indicates that stabilization of mutant p53 in tumors is crucial for its oncogenic activity, while its knockdown leads to attenuated tumor progression. However, regulatory mechanisms for mutant p53 stability or degradation remain unclear. Dr. Iwakuma has been attempting to understand the mechanisms underlying mutant p53 degradation by Hsp40/DNAJA1 knockdown and to identify compounds that deplete DNAJA1 or inhibit

DNAJA 1 activity toward including mutant p53 degradation. Importantly, DNAJA expression is frequently upregulated in human lung cancer. Elucidating a mechanism for mutant p53 degradation via DNAJA1 knockdown and identifying compounds that deplete or inhibit DNAJA1 would significantly advance our knowledge about mutant p53 stability in tumors and accelerate the development of novel therapeutic strategies for lung cancer through targeting oncogenic mutant p53.

Dr. Iwakuma's research is currently supported by National Cancer Institute and Midwest Cancer Alliance, as well as the KU Cancer Center. Dr. Iwakuma's group members have numerous opportunities to work on various basic molecular and cellular biology techniques and logics to understand the mechanisms of cancer progression and determine the biological effects of potential compounds that could cure lung cancers by targeting mutant p53.

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORSRajasingh Johnson, PhDAssistant ProfessorDepartment of Internal Medicine, Division of Cardiovascular DiseasesEmail: [email protected]

Dr. Johnson’s research interests include: safe method of reprogramming

somatic cells into  induced pluripotent stem cells (iPSCs) and their therapeutic potential in regenerative medicines;

differentiation of iPSCs into functional cardiomyocytes and its potential use in drug discovery;

studying the molecular mechanisms of reprogramming by histone deacetylation and DNA methylation;

use of adult stem cells in cardiovascular and lung vascular repair and regeneration;

use of epigenetic modifying agents in preventing sepsis-induced acute lung injury and inflammation;

studying the immunomodulatory effects of epigenetic modifying agents in macrophages during sepsis.

Michael J. Parmely, PhDProfessor, Microbiology, Molecular Genetics and ImmunologyEmail: [email protected]

The facultative intracellular bacterium Francisella tularensis is an organism that is only rarely associated with disease in human beings, but has gained a great deal of recent attention due to its potential use as a biowarfare agent. The organism is highly infectious by the pulmonary route, and a highly protective vaccine against the aerosol form of exposure does not currently exist. Recent studies have focused on gaining a more complete understanding of the pathogenesis of tularemia and defining suitable vaccine candidates.Dr. Parmely’s current research is designed to:

Identify immune correlates of protection against pulmonary and systemic tularemia;

Define the potential role of immune responses to the pathogen in the induction of host tissue damage;

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS Determine the unique features of immunity to the Type A subspecies of F. tularensis that

distinguish them from the responses to less virulent subspecies; and

Understand the basis for immune evasion by Type A F. tularensis strains

Steven Q. Simpson, MDProfessor, Division of Pulmonary and Critical Care MedicineEmail: [email protected]

Dr. Simpson’s research is focused on the condition of severe sepsis, the most deadly complication of infection, which kills more than 250,000 people every year in the United States.  He is the founder of the Midwest Critical Care Collaborative and the Kansas Sepsis Project, both of which have as their main goal, the implementation of rapid aggressive recognition and treatment of severe sepsis in hospitals throughout the region.

Dr. Simpson is involved in sepsis research on several different clinical and translational levels.  He uses the HERON database, a repository of clinical information on all KU Hospital inpatients to determine factors that affect the outcome of severe sepsis.  The database contains information on over 100,000 patients and more than 5,000 patients with severe sepsis, allowing for robust epidemiological analysis.

Dr. Simpson is also involved in prospective studies of hemodynamic changes in septic patients and how hemodynamic variables can be measured and manipulated non-invasively. Dr. Simpson and colleagues from Kansas State University have developed a mathematical model for the clinical progression of sepsis and are initiating studies to further validate the model with collection of clinical specimens and data.  

Students could find a role in any of these studies.

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2018 Parker B. Francis Summer Fellowship Program at the University of Kansas

MENTORS

Sufi Thomas, PhDAssociate ProfessorOtolaryngology and Cancer BiologyEmail: [email protected] 

Dr. Thomas has been involved in translational cancer research for over 15 years. Her research team developed a novel approach to target expression of mutant genes in tumor cells.

Traditional antisense DNA or RNA-based gene-targeted approaches cannot be administered systemically due to rapid degradation by serum enzymes. To circumvent this problem, Dr. Thomas and her collaborators developed mutation-specific guanidinium-peptide nucleic acid (GPNA) oligomers. This novel class of molecules is resistant to enzymes in serum and has a strong affinity for complementary DNA and RNA sequences. Using this approach Dr. Thomas is currently targeting oncogenic mutations in lung cancer.

Students will work under the guidance of an experienced post-doctoral fellow to test the antitumor efficacy of the mutation-specific GPNA in preclinical models of lung cancer cells. Specifically, the student will master tissue culture and molecular biology techniques and more importantly participate in the development of a cure for lung cancer.

Danny R. Welch, PhDProfessor and Chair, Department of Cancer BiologyAssociate Director for Basic Sciences and Education, University of Kansas Cancer CenterEmail: [email protected]

Dr. Welch’s lab focuses on understanding cancer metastasis, the attribute of cancer cells responsible for >90% of cancer deaths. There are multiple projects related to understanding how metastasis suppressor genes prevent development of lung metastases.

Working closely with graduate students and postdoctoral fellows, PBF fellows will have the opportunity to learn advanced molecular biology, biochemistry, cell culture and in vivo techniques. Examples include: (1) using ex vivo cultures to mimic metastasis suppressor-induced dormancy to define the molecules responsible for melanoma metastasis; (2) assessment of the capacity of fragments of metastasis suppressors to block motility, invasion and metastasis; and, (3) genetic crossing to determine mitochondrial genes that may explain racial disparities in cancer development and aggressiveness.

The Welch lab is currently supported by grants from the National Cancer Institute, Susan G. Komen for the Cure and the National Foundation for Cancer Research.

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