1 Biomedical Engineering Symposium: Cancer, Nanomedicine and ImagingRobert S. Mannel, MD Director, Stephenson Cancer Center

2 The Burden of Cancer in OklahomaFriday, December 15, 2017 The Burden of Cancer in Oklahoma 1 in 3 women and 1 in 2 men in Oklahoma will be diagnosed with cancer 19,280 new cases annually 8,100 deaths annually 172,080 cancer survivors Sources: CDC, ACS, OSDH Tumor Registry

3 Oklahoma: Cancer Mortality (7th Highest Nationally)

4 Legislative Mandate and Statewide Mission“The State Legislature requests the University of Oklahoma to establish a cancer treatment and research program to provide statewide leadership in cancer research, prevention, information and treatment, and seek to gain national recognition for excellence in the fight against cancer by being named as a designated cancer center by the National Cancer Institute.” HB 1072, passed 2001 Bipartisan-Supported Legislation 1. 2.

5 Currently 69 NCI Designated Cancer Centers in the USA State and Region Underserved by NCI-Designated Cancer Centers Currently 69 NCI Designated Cancer Centers in the US St. Louis Dallas Houston San Antonio Omaha Albuquerque Denver Kansas City Closest NCI Centers to OKC: UT - Southwestern, TX 205 miles U. of Kansas, KS miles MD Anderson, TX 445 miles Baylor U., TX miles UT - San Antonio, TX 467 miles Wash. U. / Siteman, MO 499 miles Oklahoma is one of only 15 states without an NCI Designated Cancer Center

6 The Value of an Academic Cancer CenterRaising the Standard of Cancer Care in Oklahoma through: Forging partnerships - OU, OSU, OMRF, Tulsa, OSDH, health systems, tribes, etc. Translating laboratory discoveries into better cancer therapies and diagnostics Providing patients with access to latest therapies through participation in clinical trials Providing leadership in cancer education, screening, outreach, and public health messaging

7 Assembling the Team: Increase in SCC Member ResearchersMember Home Institutions OU Health Sciences Center OU Norman OK Medical Research Foundation Oklahoma State University OU Tulsa Northeastern State University University of Central Oklahoma Oklahoma City University SW Oklahoma State Univ. Cherokee Nation The Stephenson Cancer Center’s 250 members represent: 10 institutions 20 academic colleges 60 academic departments

8 Recruitment of New ResearchersRecruitment of New Cancer Researchers The SCC has recruited 33 new cancer researchers to Oklahoma since 2012: Brought $23,309,000 in total research grant funding to OK Attained an additional $23,625,000 since arriving in OK Total funding: $46,934,000 in new out-of-state dollars to OK Recruitment with:

9 Pilot Grants to Cancer ResearchersOver the past five years the SCC has funded 116 pilot projects through seed grant and directed-funding mechanisms, totaling $6.9M FY Amount Awarded (Total) Number of Projects FY 16 2,149,661 34 FY 15 769,297 19 FY 14 1,567,033 22 FY 13 1,275,521 21 FY 12 1,201,063 20 Total 6,962,575 116 SCC pilot grants focus on: Promoting collaborative, team-based science Advancing Program Specific Aims Positioning SCC members to achieve national, peer-reviewed funding

10 NCI Funding to SCC Members (Total Cost)

11 Total Cancer-Related Funding to SCC Members (Total Cost)

12 Program Structure and Specific AimsCancer Prevention and Control Cancer health disparities Tobacco research Chemoprevention Gynecologic Cancers Molecular mechanisms in GC carcinogenesis Drug resistance Early- and late-phase clinical trials Preclinical Translational Cancer Research Cancer cell mechanisms Tumor microenvironment, metastasis and angiogenesis Nanomaterials and imaging PTCR Specific Aim 3: To develop novel tools and applications for nanomaterial and imaging technologies that enhance cancer detection, response prediction and treatment

13 Nanomedicine Applications for Cancer and other Human DiseaseDiagnosis NANOMEDICINE Treatment Detection Signaling

14 Cancer Biomedical Engineering at OU/OUHSC/SCC: Joint VentureSCC strategic steps to build cancer biomed. engineering focus: Targeted recruitment to SCC: Investigators with experience in cancer nanomedicine Rajagopal Ramesh Priyabrata Mukherjee Investment & recruitment at OU Norman Engineering - Cancer Imaging Hong Liu, Bin Zheng, Yuchen Qiu, Liangzhong Xiang (recruitment and seed funding) Engineering – Nanomaterials Roger Harrison (seed funding) Chemistry and Biochemistry Chuanbin Mao (seed funding) Collaborations with Anthony Burgett and Zhibo Yang OU Stephenson School of Biomedical Engineering Commitment to support new recruits in cancer biomedical engineering Build Infrastructure: Imaging laboratories established on both campuses. Nanotechnology Cancer Biomedicine OUHSC SCC OU-Norman Biomedical Engineering Cancer Nanomedicine

15 Cancer Nanomedicine Approach at SCCFocused Research Clinical Relevance Team Science Exosomes & miRNA miRNA Diagnosis Gold Nanoparticles Photothermal Therapy Lipid-based NPs NANOMEDICINE Gold NP-Based X-Ray fluorescence Imaging Treatment Detection Signaling Interrogating Resistance

16 Cancer Diagnosis: miRNA detection at attomolar concentration with the naked eyeGoal: Development of nanoparticles for the ultrasensitive detection of cancer biomarkers such as miRNA and p53 antibody Technology: Counting miRNA (from 10 mL suspension) by counting phage-derived plaques Team: Basic Norman – Dr. Chuanbin Mao @ SCC – Collaboration in progress Approach: Nanoparticle-based detection of low-levels miRNA in small sample volume (10 ul). Demonstrated ability to detect 6 molecules (1aM=10-18M) of miRNA visible to naked eye Advantage: Single-target let-7a miRNA counting (a-c): 0, 3, 15 aM Double-target miRNA counting (f-h): 0, 5, 20 aM each of let-7a and miR-195. Chuanbin Mao, PhD

17 Nanomaterials for cancer detection and therapyGold nanoparticles are self-therapeutic (Bhattacharya S, et.al., PNAS, 2013) Gold nanoparticles selectively absorb proteins (Giri K, et al., Bioconjugate Chem, 2014; Xiong X. et al. Oncotarget, 2014) Identification of Proteins as “Biomarkers” and “Therapeutic Targets” – Ovarian cancer as a model 7R01CA (Renewed, ) R01CA136494 Priyabrata Mukherjee (PI) Resham Bhattacharya (GC program) Katherine Moxley (GC program) Kathleen Moore (GC program) SCC Developmental Funds Biospecimen and Tissue Pathology SR Biostatistics and Research Design SR

18 Short- and Long-Term GoalsIncrease collaborations with OU Norman Continue collaborations with existing SCC members at OU Norman New School of Biomedical Engineering Continue to fund joint projects with seed grants Increase grant funding and collaborations through: Targeted recruitment Planned Conference Team-based grants R01 – Multi-PI U01 – Innovative Research in Cancer Nanotechnology (IRCN) U54 – Cancer Center Nanotechnology of Excellence (CCNE) Establish OU/SCC as Center for Cancer Nanomedicine and Imaging