IBC Meeting Minutes Boston University Location: B-406, 72 East Concord Street October 17, 2017 Start time: 12:00 PM End time: 2:55 PM

This meeting is open to the public. Present: Members: D. Stearns-Kurosawa (Chair), R. Ingalls (Vice-Chair, left 2:48 PM), R. Morales, E. Muhlberger, B. Slack, K. Tuohey, P.R. Varada, I. Afasizheva, E. Loechler (by phone, left 1:30 PM), T. Winters, C. Sulis, V. Britton (arrived 1:35 PM), J. Keeney, R. Timmerman, J. Gonsalves, J. Barton (left 12:40 PM). Guests: T. Killeen, M. Auerbach (by phone), N. Dey. Staff: S. Ghosh Absent: Members: E. Sawyer, R. Georgiadis, N. Bhadelia.

I. Review of September Meeting Minutes Recommendation: Approve For: 12 Against: 0 Abstain: 3 II. New Business

A. IBC Training Session: BSL3 and BSL4 Permit Approval Process Kevin Tuohey, Executive Director, Research Compliance outlined the permit requirements and approval processes for research requiring BSL3 or BSL4 containment. In addition to IBC approval, special permits are required from both the Centers for Disease Control and Prevention (CDC) and Boston Public Commission (BPHC) for work with risk group 3 and 4 agents. Work with non-select agent risk group 3 materials requires only a BPHC permit. The requirements for each individual permit application process were detailed. A status update of Boston University’s BSL3 and BSL4 permits with CDC and BPHC was provided.

B. Chair’s Report: None.

C. Safety Committees Report: Approved Applications/Amendments Since the last IBC meeting in September, 1 new application, 6 three-year renewals, 17 amendments and 24 annual renewals were approved.

D. Biosafety Report: Research Occupational Health Program Incident Report Since the last IBC meeting only one incident was reported to ROHP that involved biological material: An undergraduate student researcher sustained a splash of blood to her right eye when not wearing eye protection while working with two blood samples collected from donors the previous day. The donors were volunteers who were not pre-screened for blood borne infection. The student irrigated her eye immediately for 10 minutes but did not report the IBC Meeting Minutes: October 2017

exposure until several hours later. Unfortunately the source blood samples were discarded prior to the student reporting this incident. The student was counseled by the on call physician and has followed up with ROHP. Testing of the source patient is still pending. This exposure incident was reported to the BPHC.

Updates from Environmental Health & Safety At the October Laboratory Safety Committee (LSC) meeting the LSC approved a recommendation presented by the Nanomaterials subcommittee to add a section on Nanomaterials to the institutions Chemical Hygiene Plan. III. Protocol Review:

A. New Applications 1. rDNA/Bhz Protocol 2274 “Arbovirus pathogenesis in vitro” Primary Reviewer: Elke Muhlberger Secondary Reviewer: Jim Keeney Biosafety Level: BSL2 Animal Biosafety Level: N/A Campus: BUMC Applicable NIH Guidelines: Section III-D-2 and Section III-E-1 Protocol Expires: New protocol Layman’s Description: The goals of our experiment are to examine the effects of infection with arboviruses (viruses transmitted by mosquitoes) on both mosquito and mammalian cells, such as or monkey cells. We will look at the expression and protein levels in the cells during infection and determine what the virus uses or needs in the cell to complete its life cycle. We hope to identify proteins or markers that can be used to develop new treatments for infection with these arboviruses, such as dengue and Zika virus.

Meeting Comments: In this new protocol the PI is investigating the molecular mechanisms of infection of mosquito- borne viruses (also known as arboviruses), such as Zika virus or Dengue virus. To identify, validate and characterize the steps involved in the attachment and replication of the viruses in susceptible cells. They will examine the effects of deletion of specific or proteins on the host cell in the virus life cycle. Proposed work includes tissue culture, virus infection, protein and RNA expression analysis and recombinant DNA work. Work will also include analyzing patient serum samples to identify antibodies against arboviruses, some of which will be used later in neutralization experiments. The biosafety concerns and handling of biological wastes are thoroughly described. There are several minor issues (described below) that the PI needs to address.

The PI needs to: Research Project Description: Q3- Please provide statements to describe precautions are in place to make sure that pregnant staff members will not be exposed to Zika virus. Dengue and Zika virus RNAs are infectious when used to transfect cells. Please briefly describe how viral RNA-containing samples are handled to avoid accidental rescue of the virus. PPE and SE: Q7- Please add ‘fresh’ before bleach. Q8- Please add ‘fresh’ before bleach. Hazardous Biological Agent (Section A): Please remove the following agents form the list as they are not considered hazardous: Aag2 cells, BHK cells, C6/36 cells, S2 cells. Please move these cell lines to laboratory procedures section. Human and NHP cell lines are classified as BSL2. Please change appropriately. Other Potentially Infectious Material (Section B): Please provide more information about how you acquired these human serum samples (de-identified, anonymous samples from a hospital in

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Los Patios, Colombia, South America). If any IRB approval is in place from the place of origin for these samples, write this information. Recombinant DNA (Section H): Since you are making plasmid preparations for your work, the Prokaryotic Experiments section needs to be completed. Your response to question 5 is required.

LST: Lab safety training is current for all members. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 14 Against: 0 Abstain: 0

B. Three-Year Renewal Application 2. rDNA/Bhz Protocol 1248 “The pVHL/Jade-1/beta-catenin axis in renal ; Polycystin, Jade-1 and beta-catenin in cystic kidney disease; Transcription factors in renal disease and renal development” Primary Reviewer: Edward Loechler Secondary Reviewer: Rao Varada Biosafety Level: BSL2 Animal Biosafety Level: ABSL2 Campus: BUMC Applicable NIH Guidelines: Section III-D, Section III-E, Appendix B-II Protocol Expires: 11/20/2017 Layman’s Description: We are exploring some of the key genes and proteins in the kidney, in particular those involved in cancer, kidney cancer and polycystic kidney disease. Kidney cysts are fluid filled sacs that compress the surrounding kidney tissue, leading to kidney failure. Our goal is to understand the pathways involved in these diseases so that we can develop ways to treat these disorders. We have already identified a new gene and protein called Jade-1 that is involved in both kidney cancer and polycystic kidney disease, as well as colon cancer.

Meeting Comments: The Cohen laboratory is exploring key genes and proteins in the kidney, in particular those involved in kidney cancer and polycystic kidney disease. Kidney cysts are fluid filled sacs that compress the surrounding kidney tissue, leading to kidney failure. The goal is to understand the pathways involved in these diseases in order to develop new ways to treat these disorders. They have identified a new gene encoding a protein called Jade-1 that is involved in both kidney cancer and polycystic kidney disease, as well as colon cancer. The effects of Jade-1 expression, along with other pathway components, on cell growth, cell death, cell metabolism, cell differentiation, DNA repair and gene expression is being studied. Approaches include overexpressing and knocking down/out expression of Jade-1 and Jade-1 pathway components in cell culture, transgenic mice, and knockout mice, and also injecting nude mice with cultured cells to examine cell growth in a xenograft model. Jade-1 mice will also be treated with chemical carcinogens to determine if these mice are at increased risk for cancer. The protocol nicely described the scientific objectives, laboratory procedures and risk management components. The committee requested clarification on the use of yeast in the protocol and description of type and source of human tissues.

The PI needs to: Research Project Description: Q3- Please clarify the use of yeasts in the protocol. It is not clear what is the source of human tissues in the protocol. If they are not from the Biospecimen Archive Research Core (BARC), please provide more information about their source. Materials Used in Research: Please uncheck the synthetically derived nucleic acid molecule box. It does not appear that you are synthesizing any protein coding nucleic acid sequences in the laboratory. 3 | Page

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Hazardous Biological Agent (Section A): Please remove any primary human material (blood or tissues) from this list. Those should go to Section B, which you already have completed. Recombinant DNA (Section H): Please update IACUC approval date in the animal experiments section. Q3- It does not appear that you have any rDNA molecules in your protocol that is capable of expressing a pathogenic polynucleotide or polypeptide. Your answer should be ‘No’.

LST: Lab safety training is current for all members. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 14 Against: 0 Abstain: 0

A. New Applications 3. rDNA Protocol 2269 “Genetic analysis of stomatal patterning in ” Primary Reviewer: Debbie Stearns-Kurosawa Secondary Reviewer: Bob Timmerman Biosafety Level: BSL1-P Animal Biosafety Level: N/A Campus: CRC Applicable NIH Guidelines: 2016 NIH Guidelines Section III-E-2 and Appendix P-II-A Protocol Expires: New protocol Layman’s Description: Stomata are important structures on the surface of plants that facilitate gas-exchange (carbon dioxide, water vapor, oxygen) between the plant and the local environment. Understanding the relationship between stomatal patterning (both the number and arrangement of stomata on the surface) and plant physiology is important for determining how plants respond to environmental conditions. Our research is aimed at uncovering new genetic regulators that control the developmental process of stomata, and in turn, determine how the activity of those genes may affect plant physiology. This genetic regulatory network is studied using the plant model system Arabidopsis thaliana.

Meeting Comments: The goal of this new protocol is to better understand the process of stomatal development in plant physiology. To identify and understand the role of regulators of stomatal development they will perform targeted manipulations of gene expression and survey the natural genetic variation in nature that may drive differential rates of stomatal development. Their ultimate goal is to link the activity of specific genetic regulators in stomatal development with plant function and how it affects plant ecology. They will transform tumefaciens with appropriate plant gene expression constructs, which will then be used to transform the model plant Arabidopsis thaliana. Transgenic and non-transgenic plants will then be crossed to determine the effect of individual genes using physical examination and fluorescence microscopy. This is a straightforward application on plant recombinant DNA work. The committee requested procedural details on plant transformation experiment. This protocol is also being reviewed by an ad-hoc reviewer who is an expert on plant recombinant DNA work and the final approval decision will be made after all issues from all reviewers are addressed.

The PI needs to: Research Project Description: Q3- Please provide more description of the laboratory processes for introduction of genes in plants (plant transformation). Describe briefly the floral dip transformation and EMS mutagenesis process in the laboratory procedure section. Discuss briefly any biosafety considerations in the manipulation of gene expression work in plants. Lay description is too technical and in fact will be good for project description. PPE and SE: Q5- Update BSC certification date (should be 7/31/17). 4 | Page

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Q6- State briefly how the razor blades are disposed of. Materials Used in Research: Please select the highest animal biosafety level for your work (should be N/A).

LST: Lab safety training is current for both members. BUA Site Assessment: Approved Recommendation: Conditionally Approve (Administrative Review). For: 14 Against: 0 Abstain: 0

4. rDNA/Bhz Protocol 2247 “Mechanisms of Extinction Memory Enhancement for Cocaine Addiction Treatment” Primary Reviewer: Barbara Slack Secondary Reviewer: Rao Varada Biosafety Level: BSL2 Animal Biosafety Level: ABSL2 Campus: CRC Applicable NIH Guidelines: Section III-E-1 Protocol Expires: New protocol Layman’s Description: Experiments will use an animal model to study a novel treatment strategy for preventing relapse to cocaine abuse. The treatment strategy uses a combination of pharmacological and behavioral interventions. Experiments additionally will measure how memory molecules in the brain change after cocaine-addicted rats receive these treatment interventions. This research may lead to the development of new treatment drugs and to the discovery of unique behavioral therapies that inhibit relapse to cocaine abuse.

Meeting Comments: In this new protocol the PI is investigating mechanisms of memory loss and behavioral changes due to extended use of narcotics. In their study they will critically investigate the role of environmental enrichment and inhibition of glycine transporter in these behavioral abnormalities. In a rat model they will evaluate the role of glutamate receptors and neurotrophic factors in influencing learning, memory and synaptic transmission. They will utilize lentiviral vectors to modify gene expression in specific regions of the brain in rats. Drugs that specifically interfere with glutamate receptor signaling pathway will also be tested. Protocol involves injection of viral vectors in rat brain and behavioral analysis of the animals as well as extensive biochemical analysis of the brain tissues. The PI provided a clear description of the viral vectors, animal work and molecular work. Dr. Varada clarified that a biosafety cabinet is not suitable for the brain injection work as vibration from the machine will affect precision of the work. The PI needs to address a few issues listed below.

The PI needs to: Research Project Description: Q3- Please indicate briefly that bacterial culture and plasmid extractions will be done as a part of recombinant DNA work. The protocol states that a second generation lentiviral packaging system (three plasmids) from Addgene will be used. The committee recommends upgrading to a 3rd generation system to improve safety. Is there a plan for containment of animals for 48 hours after lentivirus injection? How is the drug ORG24598 prepared, administered to the animals, and disposed of? Please include a note indicating its use as a glycine transporter inhibitor. PPE and SE: Q1- Check animal handling and cage changing. Q4- Please complete this section as animals are being used in the protocol. Q5- Update BSC certification date (should be 7/31/2017). Recombinant DNA (Section H): Since plasmid vectors are being propagated in bacteria, the prokaryotic part of the table must be filled out. Please NOTE that Dr. Man also needs to complete BSL1/2 training. 5 | Page

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LST: Dr. Man needs to complete BSL1/2 training. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 0 Against: 0 Abstain: 0

B. Three-Year Renewal Applications 5. Bhz Protocol 883 “Fusion of cancer and dendritic cells as an anti-tumor vaccine” Primary Reviewer: Robin Ingalls Secondary Reviewer: Rao Varada Biosafety Level: BSL2 Animal Biosafety Level: ABSL2 Campus: BUMC Applicable NIH Guidelines: N/A Protocol Expires: 11/23/2017 Layman’s Description: of the immune system normal functions is to prevent the development of malignant diseases. However, in people who develop cancer the immune system is not successful at recognizing and destroying cancer cells. Scientists are trying to develop ways to help the body's immune system attack cancer cells. To do this, they have created a vaccine by fusing cancer cells with the natural "teacher" cells of immune system, called dendritic cells. We now assess the effect of fusion cell vaccine or its derivatives as part of combined approach in the treatment of cancer

Meeting Comments: The PI is interested in developing an anti-tumor vaccine. The strategy involves the fusion of dendritic cells (DC), (a potent antigen presenting cell) with malignant tumor cells, such as acute myelogenous leukemia, ovarian cancer cells or mouse mammary carcinoma cells. The fusion cells will then be able to elicit immune response and effectively express antibodies against the cancer cells. Dendritic cells from human or mouse blood are isolated in the laboratory. As a source of tumor cells, tissues from biopsy or tumor resection will be separated into single cells and then fused with DCs. Efficacy of these fused cells will then be analyzed in a mouse model either by injecting naïve mice followed by attempts to induce tumors in them or by injecting animals that already have tumors. The PI has provided extensive details of all laboratory procedures involved and addressed issues related to safety management. No major concerns were noted. The committee requested clarification on how human tumor samples are procured.

The PI needs to: Personnel Information: In personnel table please remove the statement on when last safety training was done. Research Laboratory Facility Information: Mention which animal facility rooms are being used in your protocol. Also if any live animal work is being done in the general research laboratory in the X-building, they should also be marked as ABSL-2. Research Project Description: Q3- Please clarify how the primary cancer cells are being collected. If they are not received through BARC core, please indicate who is collecting those samples from patients and who is bringing them to the lab. Do they have proper safety training on handling primary human materials? PPE and SE: Q4- Safety glasses must be checked off for animal work. Q5- Update BSC certification date (should be 5/13/17).

LST: PI’s lab safety training is current. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). 6 | Page

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For: 14 Against: 0 Abstain: 0

6. Bhz Protocol 1965 “HIV Aging of Immune Function” Primary Reviewer: Debbie Stearns-Kurosawa Secondary Reviewer: John Gonsalves Biosafety Level: BSL2 Animal Biosafety Level: NA Campus: BUMC Applicable NIH Guidelines: N/A Protocol Expires: 11/13/2017 Layman’s Description: We will evaluate effects of aging process and other contributing risk factors on HIV disease and immune. We will compare changes in immune system and viral measures among HIV infected who are young (less than 35yo) and older (greater than 50yo) and to uninfected counterparts. Factors, such as co-infections, lifestyle exposures (i.e., smoking, ETOH, IVDU) and HIV regimen will be examined as contributing factors in immune dysfunction.

Meeting Comments: In this clinical study, the PI proposes to investigate how the age of HIV-infected individuals influences their innate immunity and sensitivity to anti-retroviral therapies. Appropriate age- matched comparison groups of young and older uninfected individuals will also be included in the study. The overall goal of the study will be to examine how host factors (such as, age, antiretroviral therapy regimen, alcohol consumption history, drug use or other infections) and viral factors (such as, latent reservoir, residual viremia and viral load) influence HIV-induced immune dysfunction and systemic inflammation. The PI clearly describes the patient populations from whom samples will be collected. The protocol includes HLA typing, measurements of host cell telomere length, plasma HIV load, characterization of T-cell populations and measurement of inflammatory markers. This is a straightforward application. The committee requested clarification on the collection process of blood and urine samples and associated safety issues.

The PI needs to: PI Comments: Please delete comments about personnel those are no longer listed on the protocol. Research Project Description: Q3- In Laboratory Procedures section, please specify where blood will be drawn and by whom. Specify where urine will be collected and how it will be processed. Specify how blood and urine are transported to the research laboratory and by whom. PPE and SE: Q5- Update BSC certification date (should be 10/6/17). Materials Used in Research: Please contact Dr. Carol Sulis at 617-414-5037 to clarify the use of BMC clinical space and safety issues. Indicate the date of communication with her in this page. Hazardous Biological Agent (Section A): HIV is listed as a hazardous biological agent to be used in this protocol, but this is not described anywhere in procedures. Will HIV strain or clinical isolate be used in experimental procedures? If yes, describe in detail in the procedures section. If not, remove from this section Other Potentially Infectious Material (Section B): If blood or other primary human material from HIV-infected individual is being used in the protocol, such information may be included in this section instead (in addition to what you already have in the laboratory procedure section).

LST: Lab safety training for all members is current. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 14 Against: 0 Abstain: 0 7 | Page

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7. Bhz Protocol 1494 “Vasculitis Center Research Consortium” Primary Reviewer: Debbie Stearns-Kurosawa Secondary Reviewer: Bob Timmerman Biosafety Level: BSL2 Animal Biosafety Level: N/A Campus: BUMC Applicable NIH Guidelines: N/A Protocol Expires: 11/02/2017 Layman’s Description: Our studies are designed to find better ways to measure disease activity and treatment effectiveness for people suffering from vasculitis, and to determine whether particular genes play any role in the risk of developing vasculitis. Three of our studies are clinical trials designed to test the effectiveness of new treatments of vasculitis. All of these studies involve the collection and storage of blood from participants to use to study vasculitis.

Meeting Comments: In this three year renewal the PI continues to study diseases related to severe inflammation of blood vessels, also known as vasculitis. The disease is characterized by weakened blood vessels, tissue damage and rupture of blood vessels. Inflammation can also lead to thickening of the vessel wall leading to blockage of blood flow. In this study, through multiple IRB approved clinical studies, the PI’s study team is evaluating performance of several experimental drugs for the treatment of vasculitis. They also plan to identify new biomarkers and genetic risk factors. This is a multicenter study. The protocol includes analysis of blood, urine and DNA samples from patients. In one arm of the study, blood and urine samples are collected from the BMC Phlebotomy Lab. The BU Core Facility helps with the DNA extraction. The PI has described sample collection and the subsequent work flow in great detail. Safety and waste management issues are also well-described. Only a few minor administrative issues need to be addressed.

The PI needs to: Overview and Grant Funding Information: Please change the submission type to “3 Year Re- submittal”. Please remove text from the summarize changes box. This is only for amendments and annual renewals. Research Laboratory Facility Information: Please correct the BSL designation of Room E-520. BSL2 with BSL3 practice is not the appropriate designation for your work. It should be BSL2. PPE and SE: Q5- Update BSC certification date. Q10- Please remove reference to Dr. Lafyatis as he has left BU. Other Potentially Infectious Material (Section B): Please update the IRB approval dates. They should 3/23/18, 3/22/18, 3/23/18, 3/24/18, 3/16/18, 8/12/18, 8/26/18 and 9/9/18, respectively. The H-31924 is currently closed. Agreement Policy: Please check the last box regarding ROHP clearance requirement.

LST: Lab safety training for all members is current. BUA Site Assessment: To be completed, awaiting PI response. Recommendation: Conditionally Approve(Administrative Review). For: 0 Against: 0 Abstain: 0

8. rDNA/Bhz Protocol 1367 L2pB1 cell and its natural antibody in health and disease “” Primary Reviewer: Robin Ingalls Secondary Reviewer: Rao Varada Biosafety Level: BSL2 8 | Page

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Animal Biosafety Level: ABSL2 Campus: BUMC Applicable NIH Guidelines: Section III-D-4-c; Section III-D-4-c-(1); Section III-D-4-c-(2); III-E-3; III-F; App B-1 App C-VI; App E-III; App G-II-A Protocol Expires: 11/04/2017 Layman’s Description: This research project aims to study the role of L2pB1 cells in health and disease in mouse and human. Diseases including cancer, obesity, diabetes and other inflammatory conditions.

Meeting Comments: The PI is investigating the role of a specific class of B cells, called B1-B cells in anti-inflammation. B1 B cells are typically involved in a broad range of humoral immune response but do not develop into memory B cells. The lab is interested in identifying the role of a subclass of B1-B cells called L2pB1 cells in a variety of pathological conditions such as obesity, diabetes, cancer, autoimmune disease and cardiovascular diseases. Transgenic mice will be used to conditionally eliminate these cells and follow the physiological outcome. Conditional transgenic mice will be used to express the diphtheria toxin receptor in L2pB1 cells in selected tissues. DT receptors are normally absent in mice but these transgenic mice are sensitive to DT. Upon exposure to DT, the L2pB1 cells will be depleted, creating an environment where the functions of L2pB1 cells can be precisely evaluated. The Protocol also involves isolation of L2pB1 cells from human blood which will then be used for making a hybridoma cell line. Significant rDNA work is also involved in the protocol. Although minor, several issues were identified with the application as noted below, which all need to be addressed by the PI.

The PI needs to: Overview and Grant Funding Information: Please remove text from the summarize changes box. This is only for amendments and annual renewals. Research Laboratory Facility Information: Please include animal research facility rooms in the table also. Research Project Description: Q1- Please simplify the Layman’s description using non-technical words (replace the word L2pB1 with something that a non-scientific reader can understand). Q3- Please clarify what is being done with human cells and tissues in the Project Description section. It is stated that blood PBMCs will be used to develop a protocol to isolate human L2pB1 cells to create hybridoma cells, but it is not clear what will screened for in these cells. Also clarify what is the purpose of using fixed and processed human tissue from an NIH biobank in the core facilities. Remove this reference if they are not being used. Please clarify the source for the PBMCs since Dr. Nikolajczyk is no longer at BU. Note that IRB H- 27007 actually belong to Dr. Caroline Apovian. Also Rebecca and Hung are not listed in the personnel list. PPE and SE: Q1- Check animal handling and cage changing. Q5- Update BSC certification date (should be 10/31/2016). Q8- Add the word ‘fresh’ before bleach. Hazardous Biological Agent (Section A): Human lymphocyte cell line does not need IRB approval (unless it is primary material. In that case this should go to section B). Other Potentially Infectious Material (Section B): Provide IRB expiration date (This belongs to Caroline Apovian, expiry date 1/22/2018). Recombinant DNA (Section H): If plasmids are being propagated for transfection in eukaryotic cells, the prokaryotic experiments section needs to be completed.

LST: All members are current with lab safety training. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 14 Against: 0 Abstain: 0 9 | Page

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9. rDNA/Bhz Protocol 1917 “Metabolic cooperation in natural and synthetic microbial consortia” Primary Reviewer: Inna Afasizheva Secondary Reviewer: Jim Keeney Biosafety Level: BSL1 Animal Biosafety Level: N/A Campus: CRC Applicable NIH Guidelines: Exempt: Section III-F-8. Protocol Expires: 09/17/2017 Layman’s Description: Microbial communities play a fundamental role in the health of plants, animals and , and can have a huge impact on marine and terrestrial ecosystems. Appropriately modified communities could also be used for engineering applications, such as the production of biofuel from plant biomass. We are interested in understanding how interactions between different microbial species shape the diversity and the dynamics of these communities. In particular, we want to understand whether small molecules (metabolites) discarded by one organism as waste can serve as food for another organism, generating complex symbiotic interactions. We will study these interactions both in natural communities from terrestrial and marine environments, and in artificially engineered communities, built using genetically modified model organisms.

Meeting Comments: The PI is analyzing the symbiotic behavior of microorganisms in a community, which could be the or the environment we live in. In bioinformatics studies using a computer-simulated environment, he critically analyzes the role of individual organisms in maintaining symbiosis. In some of his studies he manipulates expression of specific enzyme proteins to study if an artificial environment of microbes can be generated that will be able to provide a predictable effect in the environment. The PI’s lab will make genetic manipulations on common environmental bacterial species or non-pathogenic fungi. These manipulations are expected to have the desired biological effect on for example, amino acid metabolism or cellulose degradation. The protocol involves molecular of various genes to make for example, E. coli strains that are dependent on external amino acid supply or that can make extra amino acids. In another aim they will introduce enzymes for cellulose degradation into fungi that cannot otherwise utilize cellulosic biomass of the environment. These recombinant organisms will be used to test their environmental symbiosis model. Although the protocol does not use any pathogenic microorganisms, it requires IBC approval for the recombinant DNA work. In another part of their protocol microorganisms from environmental samples will be isolated and after confirmation by ribosome sequencing that they are not pathogenic, their carbon and nitrogen source for growth will be evaluated. Laboratory procedures and biosafety issues are well-described in the protocol.

The PI needs to: Materials Used in Research: Since microorganisms that require BSL1 containment are not considered biohazard material, please remove the check mark for hazardous biological agent in section IX. However, the checkmark in Recombinant DNA box should stay. Section H (recombinant DNA) should also stay as it is now. Please note that Dr. Segre must complete the BSL1/2 training in the BioRAFT.

LST: PI needs to complete the BSL1/2 training in BioRAFT. BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 15 Against: 0 Abstain: 0

10. rDNA/Bhz Protocol 892 10 | Page

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“Molecular mechanisms of pulmonary inflammation” Primary Reviewer: Elke Muhlberger Secondary Reviewer: Rao Varada Biosafety Level: BSL2 Animal Biosafety Level: ABSL2 Campus: BUMC Applicable NIH Guidelines: Sections III-D-1, III-D-4; Appendices B-II, G-II-B, Q-II-A Protocol Expires: 11/05/2017 Layman’s Description: Lung infections are very important causes of severe disease. The proposed research is discovering how the lungs and immune system respond to the agents that cause these infections. The goal is to use these discoveries to improve the body's ability to fight off these agents and to decrease the illnesses caused by these infections.

Meeting Comments: The PI continues to investigate the mechanisms of innate immune response in the lung following infection. The response to lower respiratory tract infection usually is mediated by recruitment and activation of neutrophils at the site of infection, which often causes injury to the lung as well. Innate immune response in the lungs require the coordinated expression of diverse mediators including adhesion molecules, chemokines, colony stimulating factors, and cytokines that are either absent or present only at low levels in uninfected lungs, but are expressed at high levels during infection. The PI’s lab is engaged in dissecting the role of individual signaling pathways as well as the effect of coordinated expression of multiple mediators in lung infection or injury. In particular, they are interested in investigating the role of the NFκB pathway, STAT3 signaling pathways, as well as pathways of specific microRNAs. They will test a number of viral and bacterial pathogens known to be associated with lung infection in an animal lung infection model (in mice) and will test how individual signaling pathways are being affected. They will also use many different transgenic animals to confirm the specific roles of a particular mediator. This is a protocol that covers several lines of investigation, all related to lung infection, and attempts to find new directions for preventing acute respiratory tract infection. The PI has provided detailed descriptions of all laboratory procedures and animal infection studies with appropriate description of safety concerns and remedial actions. The protocol includes extensive recombinant DNA work including the use of lentiviral vectors. Several human cell lines as well as primary human tissues will also be used in the protocol. There are several minor points, listed below, that need to be addressed by the PI.

The PI needs to: Overview and Grant Funding Information: Please remove text from the summarize changes box. This is only for amendments and annual renewals. Research Project Description: Q3- Replace “laminar flow hoods” with “biosafety cabinets”. In contrast to BSCs, laminar flow hoods do not protect the users (2nd line under the ‘Cell culture, including in vitro and infections’ subheading, and 5th line under ‘Primary human tissues or cells’ subheading). Please indicate which commercial lentivirus systems will be used. Please briefly mention P32 use procedure in this section (remove it from the PPE section, question #1). PPE and SE: Q1- Check animal handling and cage changing. Q5- Update BSC certification date. Q7A- Please remove the description of solid wastes from Q7A (Should go to Q7B). Disinfection of surgical instruments cannot be achieved by a 30 min incubation in 70% ethanol. Dipping in 1% wescodyne or fresh 10% bleach (as appropriate) for a minimum of 30 min followed by washing and autoclaving could be an alternate. Please revise or clarify. Hazardous Biological Agent (Section A): There is redundancy in sections A and B. Please remove primary human cells form section A and the used viruses and bacteria from section B. Other Potentially Infectious Material (Section B): Remove the E. coli O6 and other viruses from this section. This section is only for primary human and NHP materials. 11 | Page

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Recombinant DNA (Section H): Please update IACUC approval date in the animal experiments section.

LST: All lab members are current with lab safety training BUA Site Assessment: Approved. Recommendation: Conditionally Approve (Administrative Review). For: 14 Against: 0 Abstain: 0

C. Amendments & Annual Renewals for Committee Review None.

IV. Approved Amendments & Annual Renewals since the last Meeting

AmE1. Protocol 1495 Title: “Oncorequisite Genes in MYC-Mediated Transformation” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add two and remove three personnel

AmE2. Protocol 1487 Title: “CLASSIFICATION OF STUDIES: 1. Human Studies-IMPAACT/ACTG 2. Human Studies-NIH, industry and internally sponsored 3. IACUC/Animal Protocols *Specific titles are listed in Section VII.” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add one and remove one personnel

AmE3. Protocol 1505 “G protein signaling circuits in health and disease” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Expedited Amendment Modification: To add MDA-MB-231, cells.

AmE4. Protocol 648 “Role of ACLP in Vascular Smooth Muscle Biology; Regulation of fibroblast and myofibroblast transitions” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-1 Type: Expedited Amendment Modification: To add one personnel

AmE5. Protocol 2174 “Polyphenols in Vascular Aging” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Expedited Amendment Modification: To add one and delete one personnel

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IBC Meeting Minutes: October 2017

AmE6. Protocol 2246 “Stem cells in lung development and disease” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To change personnel information

AmE7. Protocol 796 “Genetic and biochemical analysis of genes from Arabidopsis thaliana involved in root development and indole-3-acetic acid biosynthesis Cellular and Subcellular Resolution of the Tryptophan-Related Pathways” Biosafety Level: BSL1 Animal Biosafety Level: N/A Type: Expedited Amendment Modification: To add work involving CRISPR/Cas9 technologies in yeast

AmE8. Protocol 1487 “CLASSIFICATION OF STUDIES: 1. Human Studies-IMPAACT/ACTG 2. Human Studies-NIH, industry and internally sponsored 3. IACUC/Animal Protocols *Specific titles are listed in Section VII.” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To provide detail information on a IRB protocol that involves a clinical study with a FDA approved cholera vaccine VAXCHORA (containing live non-pathogenic V. cholerae strain) and to add one personnel

AmE9. Protocol 1495 “Oncorequisite Genes in MYC-Mediated Transformation” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add one personnel and to add new federal funding

AmE10. Protocol 1395 “Role of the NCoR corepressor complex in the regulation of inflammatory responses and insulin resistance in the adipose tissue and immune system” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add one and delete one personnel

AmE11. Protocol 1788 “Provide services related to the use of Flow Cytometer analyzer and cell sorting instruments” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add two personnel

AmE12. Protocol 1125 “The Role of Interferon Regulatory Factor 5 in the Pathogenesis of SLE” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-1 Type: Expedited Amendment Modification: To add one personnel 13 | Page

IBC Meeting Minutes: October 2017

AmE13. Protocol 1461 “1) Neural Substrates of Cognitive Decline in Aging 2) Neurobiological Consequences of Hypertension &Aging 3) Memory/Executive Function in Prefrontal & Temporal Lobe Cortex 4) Non-human Primate Model for Assessing Motor Recovery after Stroke 5) iPSC infusion as a treatment for ischemic stroke in the non-human primate” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add room 526 and to delete four personnel

AmE14. Protocol 1340 “Neuromodulation and Cortical Memory Function” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add three personnel

AmE15. Protocol 1461 “1) Neural Substrates of Cognitive Decline in Aging 2) Neurobiological Consequences of Hypertension &Aging 3) Memory/Executive Function in Prefrontal & Temporal Lobe Cortex 4) Non-human Primate Model for Assessing Motor Recovery after Stroke 5) iPSC infusion as a treatment for ischemic stroke in the non-human primate” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Expedited Amendment Modification: To add one personnel

AmE16. Protocol 1836 “Gastro-intestinal microbes degrading dietary gluten” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-1 Type: Expedited Amendment Modification: To change PI (PI leaving BU) and to delete two personnel and to delete few procedures that are no longer in use

AmR1. Protocol 2172 “Storage, Propagation and Distribution of BSL-2 Emerging Pathogens” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Amendment Review Modification: To add Nelson Bay (Pteropine orthoreovirus) to the protocol

AnR1. Protocol 1804 “Regulation of Gene Expression in the Immune System” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: No changes

AnR2. Protocol 2142 “Epithelial Stem Cells in Homeostasis and Diseases” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal 14 | Page

IBC Meeting Minutes: October 2017

Modification: No changes

AnR3. Protocol 900 “Engineering Functional Vascular Networks” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-1 Type: Annual Renewal Modification: To add three, to delete three personnel and to change primary rat endothelial cells

AnR4. Protocol 1614 “The mechanical basis of primary open angle glaucoma; Mechanism of aqueous outflow resistance in normal and glaucomatous eyes; Cellular physiology of the aqueous outflow pathway; Hydrodynamic and morphological studies of novel glaucoma devices; Evaluation of the effect of an Aerie drug (AR-13324) on aqueous flow pattern and morphology in enucleated human eyes; Cell-cell interaction in giant vacuole/pore formation; Lysosomal enzymes in outflow pathway physiology and pathophysiology” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: To add four and delete five personnel and to remove mouse glaucoma model and based therapy for glaucoma from project title

AnR5. Protocol 1043 “Mechanisms of Oxidant Signaling in Post-MI Remodeling; Oxidative Stress in Myocardial Remodeling and Failure; Reactive Oxygen Species in Patients with Heart Failure; MODIFICATION OF CARDIOVASCULAR PROTEINS BY METABOLIC DISEASE: METABOLIC PREDICTORS FOR DIASTOLIC HEART FAILURE” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: No changes

AnR6. Protocol 1545 “Mechanisms of Oxidant Signaling in Post-MI Remodeling Oxidative Stress in Myocardial Remodeling and Failure Oxidative Protein Modifications in Cardiovascular Disease” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: No changes

AnR7. Protocol 1203 “1) EXOSOME PATHWAY AS A NOVEL THERAPEUTIC TARGET OF TAUOPATHY, 2) Exosome-mediated propagation of pathogenic tau protein, 3) MICROGLIA AND EXOSOMES IN TAUOPATHY DEVELOPMENT, 4) DEVELOPMENT OF NEW PSP MOUSE MODEL, 5) EVALUATION OF STX6 SILENCING ON THE NOVEL AAV- BASED PSP MOUSE MODEL, 6) NOVEL TREM2 REPORTER PLATFORM FOR DRUG DISCOVERY, 7) Characterization of Microglial Wnt signaling in maternal immune activation-related autism, 8) Proteomic and RNA profiling of Exosomes in CTE biospecimens, 9) Targeting the miR-155 and APOE-TREM2 pathways to restore dysfunctional microglia in Alzheimers disease” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 15 | Page

IBC Meeting Minutes: October 2017

Type: Annual Renewal Modification: To add two personnel and to update grant funding title

AnR8. Protocol 901 “Effect of interstitial pressure on epithelial invasion from human mammary ducts” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To add two personnel and to add MCF-7 breast cancer cells and MCF-10A normal breast epithelial cells

AnR9. Protocol 608 “The Role of Macromolecular Assemblies in Poliovirus Replication” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To delete one personnel

AnR10. Protocol 1770 “Identification and development of biomarkers for diagnosis, monitoring and treatment of Barrett's esophagus and esophageal cancer” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To add one and delete three personnel and to modify room sharing information

AnR11. Protocol 983 “Redox control of hepatic lipid metabolism; Modification of Cardiovascular Proteins by Metabolic Disease; Aortic Stiffness in Hypertension in Obese Mice; Regulation of ischemic limb vascularization by glutaredoxin-1” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: To change personnel

AnR12. Protocol 2141 “Dissecting Long-Range Cortical Networks During Behavior” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: No changes

AnR13. Protocol 1820 “NIH R01 EB00262 Local regulation of angiogenesis by microenvironmental cues NIH R01 EB008396 Engineering Multicellular Tissue Structure, Function, and Vascularization NIH R01 HL73305 Stiffness, Cadherins, Integrins, and Mechanochemical Signaling NIH UH2 EB017103 Integrated Heart-Liver-Vascular Systems for Drug Testing in Human Health and Disease NIH R01 Mechanoelectrical interactions between cardiac myofibroblasts and myocytes NIH "Building a Human Adipose Depot" Pilot Program: Engineered human fat depots on a chip HFSP Architecture/force relationship and migration mechanics of macrophage podosomes NIH ApoE Arterial Biomechanics and Cardiovascular Disease NSF Collaborative Research: The Effects of Extracellular Matrix 16 | Page

IBC Meeting Minutes: October 2017

Alignment of Cellular Mechanotransduction in 3D Architectures PharmAkea Evaluation of LOX(L) Family Inhibitors on Matrix Remodeling in an Engineered 3D Microtissue Mechanical Testing” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: To add five and delete two personnel and to add laboratory room 521; project titles and descriptions were updated, PPE/Safety equipment updated

AnR14. Protocol 1458 “Novel Methodology for Rapid Antibiotic Susceptibility Testing in S. aureus” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To add two and delete one personnel

AnR15. Protocol 2059 “Identification of curcumin and inosine in biological specimens” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To add one personnel

AnR16. Protocol 1160 “Ikaros Regulates T-cell Fate Decisions and Leukemogenesis Generation of an Ikaros Conditional Knockout Mouse” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: No changes

AnR17. Protocol 2058 “Rapid Detection of Pathogens by Microfluidics-Based Continuous Flow qPCR” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To add two and delete one personnel

AnR18. Protocol 734 “Neurogenetic Processes in the Fetal Neocortex” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: To correct the submission type

AnR19. Protocol 609 “Structure and Function of Histone Chaperones -The Structural Basis of Protein Biogenesis -Structural Biology of Apoptosomes and Related Signaling Complexes -Structural Biology of the Type IVb Protein Secretion System of Legionella pneumophila” Biosafety Level: BSL1 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To address new DURC questions 17 | Page

IBC Meeting Minutes: October 2017

AnR20. Protocol 1035 “Novel LSF-targeted Small Molecules for Hepatocellular Carcinoma Chemotherapeutics; Transcription Factor LSF: Regulation of Cell Cycle Progression through DNA replication and Mitosis” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: No changes

AnR21. Protocol 645 “A) Calcium Influx Factor B) Ion Channels and calcium regulation C) Store- operated calcium entry and PLA2g6 in health and disease” Biosafety Level: BSL2 Animal Biosafety Level: ABSL-2 Type: Annual Renewal Modification: To add one personnel

AnR22. Protocol 485 “Molecular Basis of Skeletal Patterning in Sea Urchin ” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To add ten and remove five personnel

AnR23. Protocol 2146 “Reactivation of fetal hemoglobin as a treatment for sickle cell disease” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: To clarify lentiviral and adenoviral vector information and address new DURC questions

AnR24. Protocol 1848 “Repeat-containing RNA Binding Proteins of Trypanosomes” Biosafety Level: BSL2 Animal Biosafety Level: N/A Type: Annual Renewal Modification: No changes

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