Medical Genetics Commons^™

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M Willems, Natasha H J Ng, Juan Fernandez, Rebecca S Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Xueling Sim, Hanieh Yaghootkar, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Niels Grarup, Ruifang Li-Gao, Tibor V Varga, Jennifer L Asimit, Shuang Feng, Rona J Strawbridge, Erica L Kleinbrink, Tarunveer S Ahluwalia, Ping An, Emil V Appel, Dan E Arking, Juha Auvinen, Lawrence F Bielak, Nathan A Bihlmeyer, Jette Bork-Jensen, Jennifer A Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Järvelin, Richard A Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Man Li, Yingchang Lu, Jian'an Luan, Alisa K Manning, Jonathan Marten, Karina Meidtner, Dennis O Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M Rice, Serena Sanna, Albert Vernon Smith, Jennifer A Smith, Lorraine Southam, Heather M Stringham, Vinicius Tragante, Sander W Van Der Laan, Helen R Warren, Jie Yao, Andrianos M Yiorkas, Weihua Zhang, Wei Zhao, Mariaelisa Graff, Heather M Highland, Anne E Justice, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W Asselbergs, Lori L Bonnycastle, Michiel L Bots, Ivan Brandslund, Ji Chen, John Danesh, Renée De Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, Epic-Interact Consortium, Aliki-Eleni Farmaki, Jessica D Faul, Paul W Franks, Steve Franks, Andreas Fritsche, Anette P Gjesing, Mark O Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B Harris, Karl-Heinz Herzig, Marie-France Hivert, Torben Jørgensen, Marit E Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L R Kardia, Leena Kinnunen, Heikki A Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Lenore J Launer, Aaron Leong, Jaana Lindström, Jocelyn E Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A Nalls, Matthew Neville, James S Pankow, Alison Pattie, Eva R B Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D Taylor, Betina H Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group;, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P Bottinger, Mark J Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Francis S Collins, Josef Coresh, Francesco Cucca, Gert J De Borst, Ian J Deary, George Dedoussis, Panos Deloukas, Hester M Den Ruijter, Josée Dupuis, Michele K Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Torben Hansen, Andrew T Hattersley, Caroline Hayward, Joel N Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J F Loos, Patrick E Macdonald, Karen L Mohlke, Andrew D Morris, Patricia B Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A Peyser, Ozren Polasek, David Porteous, Michael A Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M Starr, Michael Stumvoll, Cornelia M Van Duijn, Mark Walker, Nick J Wareham, David R Weir, James G Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B Zonderman, Jerome I Rotter, Andrew P Morris, Michael Boehnke, Jose C Florez, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Robert A Scott, Anna L Gloyn, Inês Barroso

Faculty, Staff and Student Publications

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Enhancing Reciprocity, Equity And Quality Of Ethics Review For Multisite Research During Public Health Crises: The Experience Of The Covid-19 Clinical Research Coalition Ethics Working Group, Vasiliki Rahimzadeh, Jennyfer Ambe, Jantina De Vries

Center for Medical Ethics and Health Policy Staff Publications

In this paper we report findings from a commissioned report to the COVID-19 Clinical Research Coalition on approaches to streamline multinational REC review/approval during public health emergencies. As currently envisioned in the literature, a system of REC mutual recognition is theoretically possible based on shared procedural REC standards, but raises numerous concerns about perceived inequities and mistrust.

2023 Canadian Surgery Forum: Sept. 20-23, 2023, Raphaëlle Brière, Marce Émond, Axel Benhamed, Pierre-Gilles Blanchard, Sébastien Drolet, Rogeh Habashi, Bahar Golbon, Jonas Shellenberger, Jesse Pasternak, Shaila Merchant, Jonas Shellenberger, Julie La, Monakshi Sawhney, Susan Brogly, Lina Cadili, Michael Horkoff, Scott Ainslie, Jeffrey Demetrick, Brian Chai, Kevin Wiseman, Hamish Hwang, Zainab Alhumoud, Amro Salem, Rebecca Lau, Katherine Aw, Carolyn Nessim, Nada Gawad, Kameela Alibhai, Chelsea Towaij, Danielle Doan, Isabelle Raîche, Rahim Valji, Simon Turner, Patricia Nicole Balmes, Hamish Hwang, S Morad Hameed, Jun Guang Kendric Tan, Ruwan Wijesuriya, Jun Guang Kendric Tan, Nicole Lee Chui Hew, Ruwan Wijesuriya, Matthew Lund, Jeffrey Hawel, Jamie Gregor, Ken Leslie, Tori Lenet, Daniel Mcisaac, Julie Hallet, Angela Jerath, Manoj Lalu, Stuart Nicholls, Justin Presseau, Alan Tinmouth, Michael Verret, Christopher Wherrett, Dean Fergusson, Guillaume Martel, Sahil Sharma, Tyler Mckechnie, Gaurav Talwar, Janhavi Patel, Luke Heimann, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu, Christine Wang, Michael Guo, Longlong Huang, Shaun Sun, Noelle Davis, Julian Wang, Samuel Skulsky, Lindsey Sikora, Isabelle Raîche, Hyo Jin Son, Denise Gee, David Gomez, James Jung, Rajajee Selvam, Nieve Seguin, Lisa Zhang, Ariane Lacaille-Ranger, Lindsey Sikora, Daniel Mcisaac, Husein Moloo, Alicia Follett, Holly, Michael Organ, David Pace, Saba Balvardi, Pepa Kaneva, Koorosh Semsar-Kazerooni, Carmen Mueller, Melina Vassiliou, Mohammed Al Mahroos, Julio F Fiore, Kevin Schwartzman, Liane Feldman, Michael Guo, Ahmer Karimuddin, Gui Ping Liu, Trafford Crump, Jason Sutherland, Kala Hickey, Erin M Bonisteel, Jurgienne Umali, Ibrahim Dogar, Geoffrey Warden, Darrell Boone, Alexander Mathieson, Michael Hogan, David Pace, Nieve Seguin, Husein Moloo, Yiran Li, Gordon Best, Rachel Leong, Sam Wiseman, Ahmed Amine Alaoui, Roy Hajjar, Evelyne Wassef, Danny Sebastien Metellus, François Dagbert, Rasmy Loungnarath, Richard Ratelle, Frank Schwenter, Éric Debroux, Ramses Wassef, Marianne Gagnon-Konamna, Alfons Pomp, Carole S Richard, Herawaty Sebajang, Ahmed Amine Alaoui, Roy Hajjar, François Dagbert, Rasmy Loungnarath, Herawaty Sebajang, Richard Ratelle, Frank Schwenter, Éric Debroux, Ramses Wassef, Marianne Gagnon-Konamna, Alfons Pomp, Manuela M Santos, Carole S Richard, Ge Shi, Regina Leung, Christina Lim, Sarah Knowles, Simran Parmar, Christine Wang, Estifanos Debru, Fardowsa Mohamed, Megan Anakin, Yung Lee, Yasith Samarasinghe, Jigish Khamar, Bradley Petrisor, Tyler Mckechnie, Cagla Eskicioglu, Ilun Yang, Hanaa N Mughal, Mumtaz Bhugio, Muhammed A Gok, Usman A Khan, Alisha R Fernandes, Richard Spence, Geoffrey Porter, C Marius Hoogerboord, Katerina Neumann, Michal Pillar, Michael Guo, Neraj Manhas, Adrienne Melck, Tania Kazi, Tyler Mckechnie, Ghazal Jessani, Luke Heimann, Yung Lee, Dennis Hong, Cagla Eskicioglu, Tyler Mckechnie, Léa Tessier, Vicki Archer, Lily Park, Dan Cohen, Sameer Parpia, Mohit Bhandari, Joanna Dionne, Cagla Eskicioglu, Sara Bolin, Rebecca Afford, Madeleine Armstrong, Ahmer Karimuddin, Regina Leung, Ge Shi, Christina Lim, Aaron Grant, Julie Ann Van Koughnett, Sarah Knowles, Elizabeth Clement, Claire Lange, Aishwi Roshan, Ahmer Karimuddin, Tracy Scott, Kara Nadeau, Jennifer Macmillan, Jaime Wilson, Madeleine Deschenes, Aruba Nurullah, Caitlin Cahill, Victoria H Chen, Keiko M Patterson, Sam M Wiseman, Betty Wen, Joshua Bhudial, Anise Barton, Jessica Lie, Chan Mi Park, Laiji Yang, Natalia Gouskova, Dae Hyun Kim, Rebecca Afford, Sara Bolin, Dunavan Morris-Janzen, Alastair Mclellan, Ahmer Karimuddin, Victoria Archer, Zacharie Cloutier, Annie Berg, Tyler Mckechnie, Wojtek Wiercioch, Cagla Eskicioglu, Joëlle Labonté, Pascale Bisson, André Bégin, Sonia Gabriela Cheng-Oviedo, Yves Collin, Alisha R Fernandes, Intekhab Hossain, James Ellsmere, Charbel El-Kefraoui, Uyen Do, Andrew Miller, Araz Kouyoumdjian, David Cui, Elahe Khorasani, Tara Landry, Alexandre Amar-Zifkin, Lawrence Lee, Liane Feldman, Julio Fiore, Tran Michelle Au, Mark Oppenheimer, Sarvesh Logsetty, Raghad Alshammari, Mohammad Alabri, Ahmer Karimuddin, Carl Brown, Manoj J Raval, Paul Terry Phang, Samantha Bird, Zarrukh Baig, Nawaf Abu-Omar, Dilip Gill, Soumiya Suresh, Nathan Ginther, Marta Karpinski, Amandeep Ghuman, Peter R A Malik, Kameela Alibhai, Taryn Zabolotniuk, Isabelle Raîche, Nada Gawad, Sarah Mashal, Nathalie Boulanger, Larry Watt, Tarek Razek, Paola Fata, Jeremy Grushka, Evan G Wong, Intekhab Hossain, Maxim Landry, Sarah Mackey, Nicholas Fairbridge, Alison Greene, Mark Borgoankar, Cullen Kim, Diana Decarvalho, David Pace, Robin Wigen, Emily Walser, Jacob Davidson, Michael Dorward, Leanne Muszynski, Celia Dann, Natashia Seemann, Jennifer Lam, Kaitlyn Harding, A J Lowik, Caroline Guinard, Sam Wiseman, Odelle Ma, Valentin Mocanu, Andrea Lin, Shahzeer Karmali, David Bigam, Kaitlyn Harding, Grant Greaves, Brent Parker, Vu Nguyen, Azim Ahmed, Belinda Yee, Joël Perren, Mathew Norman, Morgan Grey, Rafael Perini, Fahd Jowhari, Adrian Bak, Jeremy Drung, Laura Allen, Daniele Wiseman, Bradley Moffat, Jeremy K H Lee, Catherine Mcguire, Isabelle Raîche, Mihaela Tudorache, Nada Gawad, Lily J Park, Flavia K Borges, Rahima Nenshi, Michael Jacka, Diane Heels-Ansdell, Marko Simunovic, Jessica Bogach, Pablo E Serrano, Lehana Thabane, P J Devereaux, Sauleha Farooq, Erica Lester, Janice Kung, Nori Bradley, Gordon Best, San Ahn, Lisa Zhang, Nicole Prince, Olivia Cheng-Boivin, Nieve Seguin, Harry Wang, Liam Quartermain, Sherry Tan, Jennifer Shamess, Mathilde Simard, Humberto Vigil, Isabelle Raîche, Mary Hanna, Husein Moloo, Riordan Azam, Gary Ko, Mayanne Zhu, Yanuga Raveendran, Christine Lam, Janet Tang, Amrit Bajwa, Marina Englesakis, Emma Reel, Jordan Cleland, Laura Snell, Gianni Lorello, Tulin Cil, Hilalion San Ahn, Catherine Dube, Daniel Mcisaac, David Smith, Alexie Leclerc, Jennifer Shamess, Alaa Rostom, Natalia Calo, Kednapa Thavorn, Husein Moloo, Simon Laplante, Louis Liu, Nadia Khan, Allan Okrainec, Odelle Ma, Andrea Lin, Valentin Mocanu, Shahzeer Karmali, David Bigam, Gladys Bruyninx, Ilinca Georgescu, Vladislav Khokhotva, Gaurav Talwar, Sahil Sharma, Tyler Mckechnie, Shuling Yang, Jigish Khamar, Dennis Hong, Aristithes Doumouras, Cagla Eskicioglu, Karina Spoyalo, Thais Ayres Rebello, Gyan Chhipi-Shrestha, Kelly Mayson, Rehan Sadiq, Kasun Hewage, Andrea Macneill, Susan Muncner, Mo Yu Li, Igor Mihajlovic, Mark Dykstra, Ryan Snelgrove, Haili Wang, Christina Schweitzer, Sam M Wiseman, Ivneet Garcha, Uzair Jogiat, Vickie Baracos, Simon R Turner, Dean Eurich, Heather Filafilo, Armin Rouhi, Alexandre Bédard, Eric L R Bédard, Yogita S Patel, Jacob A Alaichi, John Agzarian, Wael C Hanna, Yogita S Patel, Jacob A Alaichi, Esther Provost, Bobby Shayegan, Anthony Adili, Wael C Hanna, Nikkita Mistry, Anthony A Gatti, Yogita S Patel, Forough Farrokhyar, Feng Xie, Wael C Hanna, Kerrie A Sullivan, Forough Farrokhyar, Yogita S Patel, Moishe Liberman, Simon R Turner, Anne V Gonzalez, Rahul Nayak, Kazuhiro Yasufuku, Wael C Hanna, Nikkita Mistry, Anthony A Gatti, Yogita S Patel, Sam Cross, Forough Farrokhyar, Feng Xie, Wael C Hanna, Pier-Luc Haché, Geraud Galvaing, Serge Simard, Jocelyn Grégoire, Jean Bussières, Yves Lacasse, Sami Sassi, Catherine Champagne, Anne-Sophie Laliberté, Jin Yong Jeong, Uzair Jogiat, Hillary Wilson, Alexandre Bédard, Pam Blakely, Jerry Dang, Warren Sun, Shahzeer Karmali, Eric L R Bédard, Clarence Wong, Suhail Yaqoob Hakim, Samim Azizi, Ayman El-Menyar, Sandro Rizoli, Hassan Al-Thani, Alisha R Fernandes, Daniel French, Chao Li, James Ellsmere, Shiloh Gossen, Daniel French, Jon Bailey, Phil Tibbo, Candice Crocker, Adom Bondzi-Simpson, Tiago Ribeiro, Biniam Kidane, Michael Ko, Natalie Coburn, Girish Kulkarni, Julie Hallet, Ahmed Faidh Ramzee, Ibrahim Afifi, Mushrek Alani, Ayman El-Menyar, Sandro Rizoli, Hassan Al-Thani, Talat Chughtai, Bright Huo, Daria Manos, Zhaolin Xu, Katerina-Maria Kontouli, Samuel Chun, John Fris, Allison M R Wallace, Daniel G French, Catherine Giffin, Moishe Liberman, Gabriel Dayan, Anne-Sophie Laliberté, Kazuhiro Yasufuku, Alexander Farivar, Biniam Kidane, Cara Weessies, Madeline Robinson, Leeann Bednarek, Gordon Buduhan, Richard Liu, Lawrence Tan, Sadeesh K Srinathan, Biniam Kidane, Awrad Nasralla, Najib Safieddine, Sayf Gazala, Carmine Simone, Negar Ahmadi, Roy Hilzenrat, Maurice Blitz, Shaun Deen, Michael Humer, Anand Jugnauth, Gordon Buduhan, Laura Kerr, Simon Sun, Ikennah Browne, Yogita Patel, Wael Hanna, Brandon Loshusan, Arefin Shamsil, Michael D Naish, Mehdi Qiabi, Rahul Nayak, Rajni Patel, Richard Malthaner, Patel Pooja, Ribeiro Roberto, Hirsch Greg, French Daniel, Caroline Huynh, Sohat Sharma, Arthur Vieira, Fagun Jain, Yejun Lee, Dorsa Mousa-Doust, Jonice Costa, Michelle Mezei, Kristine Chapman, Hannah Briemberg, Kristin Jack, Kyle Grant, James Choi, John Yee, Anna L Mcguire, Sami Aftab Abdul, Francois Khazoom, Katherine Aw, Rebecca Lau, Sebastien Gilbert, Sudhir Sundaresan, Daniel Jones, Andrew J E Seely, Patrick J Villeneuve, Donna E Maziak, Claudie-Anne Pigeon, Jonathan Frigault, Sébastien Drolet, Ève-Marie Roy, Kristopher Bujold-Pitre, Valérie Courval, Lea Tessier, Tyler Mckechnie, Yung Lee, Lily Park, Nirupa Gangam, Cagla Eskicioglu, Zacharie Cloutier, Tyler Mckechnie, Victoria Archer, Lily Park, Jay Lee, Ashaka Patel, Dennis Hong, Cagla Eskicioglu, Simarpreet Ichhpuniani, Tyler Mckechnie, Geoffrey Elder, Andrew Chen, Kathleen Logie, Aristithes Doumouras, Dennis Hong, Randy Benko, Cagla Eskicioglu, Matthew Castelo, Lawrence Paszat, Bettina Hansen, Adena Scheer, Neil Faught, Lena Nguyen, Nancy Baxter, Sahil Sharma, Tyler Mckechnie, Jigish Khamar, Kathy Wu, Cagla Eskicioglu, Tyler Mckechnie, Jigish Khamar, Yung Lee, Léa Tessier, Edward Passos, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu, Tyler Mckechnie, Jigish Khamar, Anjali Sachdeva, Yung Lee, Dennis Hong, Cagla Eskicioglu, Linda Y N Fei, Antonio Caycedo, Sunil Patel, Teodora Popa, Lee Boudreau, Andrea Grin, Tao Wang, Jessica Lie, Ahmer Karimuddin, Carl Brown, Terry Phang, Manoj Raval, Amandeep Ghuman, Sydney Candy, Kareena Nanda, Christine Li, Ryan Snelgrove, Mark Dykstra, Karen Kroeker, Haili Wang, Haven Roy, Ramzi M Helewa, Garrett Johnson, Harminder Singh, Eric Hyun, Dana Moffatt, Ashley Vergis, Patricia Balmes, Terry Phang, Michael Guo, Jerry Liu, Haven Roy, Sandra Webber, Farhana Shariff, Ramzi M Helewa, Dave Hochman, Jason Park, Garrett Johnson, Eric Hyun, Stephan Robitaille, Anna Wang, Michael Maalouf, Naser Alali, Hiba Elhaj, Sender Liberman, Patrick Charlebois, Barry Stein, Liane Feldman, Julio F Fiore, Lawrence Lee, Richard Hu, Ariane Lacaille-Ranger, San Ahn, Mihaela Tudorache, Husein Moloo, Lara Williams, Isabelle Raîche, Reilly Musselman, Maddy Lemke, Laura Allen, Nadeesha Samarasinghe, Kelly Vogt, Muriel Brackstone, Terry Zwiep, Elizabeth Clement, Claire Lange, Armaghan Alam, Anu Ghuman, Ahmer Karimuddin, Terry Phang, Manoj Raval, Carl Brown, Elizabeth Clement, Jerry Liu, Anu Ghuman, Ahmer Karimuddin, Terry Phang, Manoj Raval, Carl Brown, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Hanaa N Mughal, Muhammed A Gok, Usman A Khan, Nicholas James, Terry Zwiep, Julie Ann Van Koughnett, Dora Laczko, Tyler Mckechnie, Shuling Yang, Kathy Wu, Sahil Sharma, Yung Lee, Lily Park, Aristithes Doumouras, Dennis Hong, Sameer Parpia, Mohit Bhandari, Cagla Eskicioglu, Tyler Mckechnie, Léa Tessier, Stephanie Lee, Tania Kazi, Praveen Sritharan, Yung Lee, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu, Tyler Mckechnie, Yung Lee, Dennis Hong, Joanna Dionne, Aristithes Doumouras, Sameer Parpia, Mohit Bhandari, Cagla Eskicioglu, Olivia Hershorn, Amandeep Ghuman, Ahmer Karimuddin, Carl Brown, Manoj Raval, P Terry Phang, Alex Chen, Marylise Boutros, Natasha Caminsky, Teodora Dumitra, Sarah Faris-Sabboobeh, Marie Demian, Georgia Rigas, Olivia Monton, Allister Smith, Jeongyoon Moon, Marie Demian, Richard Garfinkle, Carol-Ann Vasilevsky, Fateme Rajabiyazdi, Marylise Boutros, Emily Courage, Danielle Leblanc, Matthew Benesch, Kala Hickey, Katia Hartwig, Casey Armstrong, Reniel Engelbrecht, Mitchell Fagan, Mark Borgaonkar, David Pace, Jessica Shanahan, Jeongyoon Moon, Ebram Salama, Anna Wang, Mylène Arsenault, Nathalie Leon, Carmen Loiselle, Fatemeh Rajabiyazdi, Marylise Boutros, Kelly Brennan, Mandip Rai, Ameer Farooq, Chad Mcclintock, Weidong Kong, Sunil Patel, Neyla Boukhili, Natasha Caminsky, Sarah Faris-Sabboobeh, Marie Demian, Marylise Boutros, Tiffany Paradis, Stephan Robitaille, Teodora Dumitra, A Sender Liberman, Patrick Charlebois, Barry Stein, Julio F Fiore, Liane S Feldman, Lawrence Lee, Terry Zwiep, Deborah Abner, Tarik Alam, Elaine Beyer, Michele Evans, Mary Hill, Debra Johnston, Karla Lohnes, Svea Menard, Nicole Pitcher, Kelly Sair, Bev Smith, Bonita Yarjau, Kimberly Leblanc, Nadeesha Samarasinghe, Ahmer A Karimuddin, Carl J Brown, P Terry Phang, Manoj J Raval, Karen Macdonell, Amandeep Ghuman, Alexandra Harvey, P Terry Phang, Ahmer Karimuddin, Carl J Brown, Manoj J Raval, Amandeep Ghuman, Olivia Hershorn, Amandeep Ghuman, Ahmer Karimuddin, Manoj Raval, P Terry Phang, Carl Brown, Kathleen Logie, Tyler Mckechnie, Yung Lee, Dennis Hong, Cagla Eskicioglu, Mirna Matta, Laura Baker, Jessica Hopkins, Ryan Rochon, Donald Buie, Anthony Maclean, Amandeep Ghuman, Jason Park, Ahmer A Karimuddin, P Terry Phang, Manoj J Raval, Carl J Brown, Ameer Farooq, Amandeep Ghuman, Sunil Patel, Hugh Macdonald, Ahmer Karimuddin, Manoj Raval, P Terry Phang, Carl Brown, Vanessa Wiseman, Kelly Brennan, Sunil Patel, Ameer Farooq, Shaila Merchant, Weidong Kong, Chad Mcclintock, Chris Booth, Tim Hann, Alessandro Ricci, Sunil Patel, Kelly Brennan, Vanessa Wiseman, Chad Mcclintock, Weidong Kong, Ameer Farooq, Rohan Kakkar, Olivia Hershorn, Manoj Raval, P Terry Phang, Ahmer Karimuddin, Amandeep Ghuman, Carl Brown, Vanessa Wiseman, Ameer Farooq, Sunil Patel, Roy Hajjar, Emmanuel Gonzalez, Gabriela Fragoso, Manon Oliero, Ahmed Amine Alaoui, Hervé Vennin Rendos, Souad Djediai, Thibault Cuisiniere, Patrick Laplante, Claire Gerkins, Ayodeji Samuel Ajayi, Khoudia Diop, Nassima Taleb, Sophie Thérien, Frédéricke Schampaert, Hefzi Alratrout, François Dagbert, Rasmy Loungnarath, Herawaty Sebajang, Frank Schwenter, Ramses Wassef, Richard Ratelle, Éric Debroux, Jean-François Cailhier, Bertrand Routy, Borhane Annabi, Nicholas J B Brereton, Carole Richard, Manuela M Santos, Tamara Gimon, Helen Macrae, Anthony De Buck Van Overstraeten, Mantaj Brar, Sami Chadi, Erin Kennedy, Laura Baker, Jessica Hopkins, Ryan Rochon, Donald Buie, Anthony Maclean, Lily J Park, Victoria Archer, Tyler Mckechnie, Yung Lee, Daniel Mcisaac, Pavel Rashanov, Cagla Eskicioglu, Husein Moloo, P J Devereaux, Rehab Alsayari, Tyler Mckechnie, Simarpreet Ichhpuniani, Yung Lee, Cagla Eskicioglu, Roy Hajjar, Manon Oliero, Gabriela Fragoso, Ayodeji Samuel Ajayi, Ahmed Amine Alaoui, Hervé Vennin Rendos, Annie Calvé, Thibault Cuisinière, Claire Gerkins, Sophie Thérien, Nassima Taleb, François Dagbert, Herawaty Sebajang, Rasmy Loungnarath, Frank Schwenter, Richard Ratelle, Ramses Wassef, Eric Debroux, Carole Richard, Manuela M Santos, Erin Kennedy, Marko Simunovic, Selina Schmocker, Carl Brown, Anthony Maclean, Sender Liberman, Sébastien Drolet, Katerina Neumann, Peter Stotland, Kartik Jhaveri, Richard Kirsch, Hafssah Alnajem, Huseen Alibrahim, Christian Giundi, Alex Chen, Georgia Rigas, Haroon Munir, Ali Safar, Sarah Sabboobeh, Jessica Holland, Marylise Boutros, Erin Kennedy, Carole Richard, Marko Simunovic, Selina Schmocker, Carl Brown, Anthony Maclean, Sender Liberman, Sébastien Drolet, Katerina Neumann, Peter Stotland, Kartik Jhaveri, Richard Kirsch, Gladys Bruyninx, Dilip Gill, Rehab Alsayari, Tyler Mckechnie, Yung Lee, Dennis Hong, Cagla Eskicioglu, Lisa Zhang, Sean Abtahi, Allison Chhor, Gordon Best, Isabelle Raîche, Reilly Musselman, Lara Williams, Husein Moloo, Natasha Grace Caminsky, Jenny Jeongyoon Moon, Daniel Marinescu, Allison Pang, Carol-Ann Vasilevsky, Marylise Boutros, Mohammed Al-Abri, Elliott Gee, Ahmer Karimuddin, P Terry Phang, Carl Brown, Manoj Raval, Amandeep Ghuman, Nina Morena, Libby Ben-Zvi, Victoria Hayman, Mary Hou, Diana Nguyen, Carrie A Rentschler, Ari N Meguerditchian, Zuhaib Mir, Linda Fei, Sandra Mckeown, Rachelle Dinchong, Nicholas Cofie, Nancy Dalgarno, Rona Cheifetz, Shaila Merchant, Alisha Jaffer, Carolyn Cullinane, Gerard Feeney, Amirhossein Jalali, Anne Merrigan, Chwanrow Baban, Juliette Buckley, Shona Tormey, Matthew Benesch, Rongrong Wu, Kazuaki Takabe, Matthew Benesch, Shalana O'Brien, Karineh Kazazian, Ali Hosni Abdalaty, Christine Brezden, Ron Burkes, Eric Chen, Anand Govindarajan, Raymond Jang, Erin Kennedy, Jelena Lukovic, Aruz Mesci, Fayez Quereshy, Carol Swallow, Sami Chadi, Rogeh Habashi, Jesse Pasternak, Wanda Marini, Weiyue Zheng, Kiichi Murakami, Pamela Ohashi, Michael Reedijk, Richard Hu, Victoria Ivankovic, Lewis Han, Louise Gresham, Ranjeeta Mallick, Rebecca Auer, Tiago Ribeiro, Adom Bondzi-Simpson, Natalie Coburn, Julie Hallet, Tulin Cil, Adam Fontebasso, Alex Lee, Ericka Bernard-Bedard, Boaz Wong, Heidi Li, Elysia Grose, Olivier Brandts-Longtin, Katie Aw, Rebecca Lau, Ahmad Abed, James Stevenson, Rahat Sheikh, Richard Chen, Stephanie Johnson-Obaseki, Carolyn Nessim, Rachel Liu Hennessey, Adam T Meneghetti, Michael Bildersheim, Antoine Bouchard-Fortier, Gregg Nelson, Lloyd Mack, Farhad Ghasemi, Mahtab Malekian Naeini, Armen Parsyan, Yuvreet Kaur, Andrea Covelli, Fayez Quereshy, Elena Elimova, Elan Panov, Jelena Lukovic, James Brierley, Bev Burnett, Carol Swallow, Ashley Eom, David Kirkwood, Nicole Hodgson, Aristithes Doumouras, Jessica Bogach, Timothy Whelan, Mark Levine, Elena Parvez, Deanna Ng, Karineh Kazazian, Kiera Lee, Yi Qing Lu, Dae Kyum Kim, Marco Magalhaes, Emma Grigor, Angel Arnaout, Jing Zhang, Elliott K Yee, Julie Hallet, Nicole J Look Hong, Lena Nguyen, Natalie Coburn, Frances C Wright, Sonal Gandhi, Katarzyna J Jerzak, Andrea Eisen, Amanda Roberts, Daniel Ben Lustig, May Lynn Quan, Tien Phan, Antoine Bouchard-Fortier, Jeff Cao, Conrad Bayley, Akie Watanabe, Susan Yao, Eitan Prisman, Gary Groot, Elliot Mitmaker, Ross Walker, Jonn Wu, Jesse Pasternak, Chi Kien Lai, Antoine Eskander, Jonathan Wasserman, Frederic Mercier, Kathryn Roth, Sabrina Gill, Carlos Villamil, David Goldstein, Vicki Munro, Alok Pathak, Debon Lee, Anne Nguyen, Sam Wiseman, Luckshi Rajendran, Marco Claasen, Tommy Ivanics, Nazia Selzner, Ian Mcgilvray, Mark Cattral, Anand Ghanekar, Carol-Anne Moulton, Trevor Reichman, Chaya Shwaartz, Ur Metser, Ron Burkes, Erin Winter, Steven Gallinger, Gonzalo Sapisochin, Juan Glinka, Evelyn Waugh, Ken Leslie, Anton Skaro, Epharaim Tang, Juan Glinka, Janyssa Charbonneau, Alexandre Brind'amour, Alexis F Turgeon, Sarah O'Connor, Thomas Couture, Yifan Wang, Osamu Yoshino, Michael Driedger, Michael Beckman, Dionisios Vrochides, John Martinie, Abdulrahman Alabduljabbar, Maral Aali, Christopher Lightfoot, Boris Gala-Lopez, Maud Labelle, Frédérick D'Aragon, Yves Collin, Dhruvin Hirpara, Jonathan Irish, Mohammed Rashid, Tharsiya Martin, Alice Zhu, Leah Mcknight, Amber Hunter, Shiva Jayaraman, Alice Wei, Natalie Coburn, Frances Wright, Katlin Mallette, Ahmad Elnahas, Nawar Alkhamesi, Christopher Schlachta, Jeffrey Hawel, Ephraim Tang, Subin Punnen, Jade Zhong, Yuwei Yang, Lucas Streith, Jordan Yu, Stephen Chung, Peter Kim, Stephanie Chartier-Plante, Maja Segedi, Michael Bleszynski, Molly White, Melanie E Tsang, Shiva Jayaraman, Kimberley Lam-Tin-Cheung, Shiva Jayaraman, Melanie Tsang, Brittany Greene, Panthea Pouramin, Susan Allen, David Evan Nelson, Mark Walsh, Julien Côté, Rolando Rebolledo, Mélanie Borie, Ahmed Menaouar, Carolyne Landry, Marylène Plasse, Richard Létourneau, Michel Dagenais, Zhixia Rong, André Roy, Eve Beaudry-Simoneau, Franck Vandenbroucke-Menu, Réal Lapointe, Pasquale Ferraro, Shant Der Sarkissian, Nicolas Noiseux, Simon Turcotte, Yara Haddad, Antoine Bernard, Clara Lafortune, Nathalie Brassard, Annie Roy, Claude Perreault, Gaétan Mayer, Mieczyslaw Marcinkiewicz, Majambu Mbikay, Michel Chrétien, Simon Turcotte, Evelyn Waugh, Lynne Sinclair, Juan Glinka, Elizabeth Shin, Crystal Engelage, Ephraim Tang, Anton Skaro, Hala Muaddi, Jennifer Flemming, Bettina Hansen, Laura Dawson, Grainne O'Kane, Jordan Feld, Gonzalo Sapisochin, Alice Zhu, Shiva Jayaraman, Sean Cleary, Anthonie Hamel, Claudie-Anne Pigeon, Camille Marcoux, Thanh-Quan Philips Ngo, Isabelle Deshaies, Sarah Mansouri, Nawal Amhis, Maxime Léveillé, Christine Lawson, Carol Achard, Carolina Ilkow, Yves Collin, Lee-Hwa Tai, Lily Park, Christopher Griffiths, Daniel D'Souza, Felipe Rodriguez, Tyler Mckechnie, Pablo E Serrano, Rachel Liu Hennessey, Yuwei Yang, Adam T Meneghetti, O Neely M Panton, Chieh Jack Chiu, Oscar Henao, Fernando Spencer Netto, Marguerite Mainprize, Rachel Liu Hennessey, Chieh Jack Chiu, Rachel Liu Hennessey, Chieh Jack Chiu, Sukhdeep Jatana, Kevin Verhoeff, Valentin Mocanu, Uzair Jogiat, Daniel Birch, Shahzeer Karmali, Noah Switzer, Alexandra Hetherington, Kevin Verhoeff, Valentin Mocanu, Daniel Birch, Shahzeer Karmali, Noah Switzer, Ali Safar, Najla Al-Ghaithi, Phil Vourtzoumis, Sebastian Demyttenaere, Olivier Court, Amin Andalib, Hillary Wilson, Kevin Verhoeff, Jerry Dang, Janice Kung, Noah Switzer, Daniel Birch, Karen Madsen, Shahzeer Karmali, Valentin Mocanu, Ted Wu, Wenjing He, Ashley Vergis, Krista Hardy, Marta Zmudzinski, Felica Daenick, Janice Linton, Marta Zmudzinski, Melinda Fowler-Woods, Wenjing He, Amanda Fowler-Woods, Geraldine Shingoose, Ashley Vergis, Krista Hardy, Yung Lee, Aristithes Doumouras, Amber Molnar, Francis Nguyen, Dennis Hong, Romano Schneider, Andras B Fecso, Priya Sharma, Azusa Maeda, Timothy Jackson, Allan Okrainec, Cheynne Mclean, Valentin Mocanu, Daniel Birch, Shahzeer Karmali, Noah Switzer, Sarah Macvicar, Jerry Dang, Valentin Mocanu, Kevin Verhoeff, Uzair Jogiat, Shahzeer Karmali, Daniel Birch, Noah Switzer, Steffane Mclennan, Kevin Verhoeff, Kieran Purich, Jerry Dang, Janice Kung, Valentin Mocanu, Steffane Mclennan, Kevin Verhoeff, Valentin Mocanu, Uzair Jogiat, Daniel W Birch, Shahzeer Karmali, Noah J Switzer, Lisa Jeffery, Hamish Hwang, Alexis Ryley, Morgan Schellenberg, Natthida Owattanapanich, Brent Emigh, Chance Nichols, Joshua Dilday, Chaiss Ugarte, Atsushi Onogawa, Kazuhide Matsushima, Matthew J Martin, Kenji Inaba, Morgan Schellenberg, Brent Emigh, Chance Nichols, Joshua Dilday, Chaiss Ugarte, Atsushi Onogawa, Doug Shapiro, Daniel Im, Kenji Inaba, Morgan Schellenberg, Natthida Owattanapanich, Chaiss Ugarte, Lydia Lam, Matthew J Martin, Kenji Inaba, Joao Rezende-Neto, Sunil Patel, Lisa Zhang, Zuhaib Mir, Madeline Lemke, William Leeper, Laura Allen, Eric Walser, Kelly Vogt, Tiago Ribeiro, Sarah Bateni, Adom Bondzi-Simpson, Natalie Coburn, Julie Hallet, Victoria Barabash, Austin Barr, Wing Chan, Suhail Yaqoob Hakim, Ayman El-Menyar, Sandro Rizoli, Hassan Al-Thani, Hanaa N Mughal, Mumtaz Bhugio, Muhammed A Gok, Usman A Khan, Ahmed Warraich, Lawrence Gillman, Markus Ziesmann, Jovana Momic, Nouf Yassin, Mella Kim, Amy Makish, Eric Walser, Shane Smith, Ian Ball, Brad Moffat, Neil Parry, Kelly Vogt, Alex Lee, Jenna Kroeker, David Evans, Nahal Fansia, Chana Notik, Evan G Wong, Guire Coyle, David Seben, Jaiden Smith, Brandy Tanenbaum, Corey Freedman, Avery Nathens, Robert Fowler, Prachikumari Patel, Tim Elrick, Meghan Ewing, Steven Di Marco, Tarek Razek, Jeremy Grushka, Evan G Wong, Lily J Park, Flavia K Borges, Rahima Nenshi, Pablo E Serrano, Paul Engels, Kelly Vogt, Emily Di Sante, Jessica Vincent, Kate Tsiplova, P J Devereaux, Gaurav Talwar, Joanna Dionne, Tyler Mckechnie, Yung Lee, Tania Kazi, Abdullah El-Sayes, Jessica Bogach, Dennis Hong, Cagla Eskicioglu, Matthew Connell, Amanda Klooster, Jenna Beck, Kevin Verhoeff, Matt Strickland, Ram Anantha, Lilly Groszman, Natasha G Caminsky, Larry Watt, Nathalie Boulanger, Tarek Razek, Jeremy Grushka, Steven Di Marco, Evan G Wong, Rachel Livergant, Brooke Mcdonald, Catherine Binda, Shreya Luthra, Nicole Ebert, Ryan Falk, Emilie Joos

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Student Publications

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

Research design and methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Cerebellar Dysfunction In Rodent Models With Dystonia, Tremor, And Ataxia, Meike E Van Der Heijden, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a movement disorder characterized by involuntary co- or over-contractions of the muscles, which results in abnormal postures and movements. These symptoms arise from the pathophysiology of a brain-wide dystonia network. There is mounting evidence suggesting that the cerebellum is a central node in this network. For example, manipulations that target the cerebellum cause dystonic symptoms in mice, and cerebellar neuromodulation reduces these symptoms. Although numerous findings provide insight into dystonia pathophysiology, they also raise further questions. Namely, how does cerebellar pathophysiology cause the diverse motor abnormalities in dystonia, tremor, and ataxia? Here, we describe recent work in rodents …

3pnmf-Mkl: A Non-Negative Matrix Factorization-Based Multiple Kernel Learning Method For Multi-Modal Data Integration And Its Application To Gene Signature Detection\, Saurav Mallik, Anasua Sarkar, Sagnik Nath, Ujjwal Maulik, Supantha Das, Soumen Kumar Pati, Soumadip Ghosh, Zhongming Zhao

Faculty, Staff and Student Publications

In this current era, biomedical big data handling is a challenging task. Interestingly, the integration of multi-modal data, followed by significant feature mining (gene signature detection), becomes a daunting task. Remembering this, here, we proposed a novel framework, namely, three-factor penalized, non-negative matrix factorization-based multiple kernel learning with soft margin hinge loss (3PNMF-MKL) for multi-modal data integration, followed by gene signature detection. In brief, limma, employing the empirical Bayes statistics, was initially applied to each individual molecular profile, and the statistically significant features were extracted, which was followed by the three-factor penalized non-negative matrix factorization method used for data/matrix fusion …

Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz

Theses and Dissertations

The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the Kras^G12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …

Within Subject Cross-Tissue Analyzes Of Epigenetic Clocks In Substance Use Disorder Postmortem Brain And Blood, Brenda Cabrera-Mendoza, Laura Stertz, Katherine Najera, Sudhakar Selvaraj, Antonio L Teixeira, Thomas D Meyer, Gabriel R Fries, Consuelo Walss-Bass

Faculty, Staff and Student Publications

There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown. In this study, we evaluated multiple epigenetic clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBlood, DNAmPhenoAge, DNAmGrimAge, and DNAmTL) in individuals with SUD (n = 42), including alcohol (n = 10), opioid (n = 19), and stimulant use disorder (n = 13), and controls (n = 10) in …

Novel Compound Heterozygous Variants In The Ush2a Gene Associated With Autosomal Recessive Retinitis Pigmentosa Without Hearing Loss, Yanxia Huang, Lamei Yuan, Guiyun He, Yanna Cao, Xiong Deng, Hao Deng

Faculty, Staff and Student Publications

Background: Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies characterized by the primary degeneration of rod photoreceptors and the subsequent loss of cone photoreceptors because of cell death. It is caused by different mechanisms, including inflammation, apoptosis, necroptosis, pyroptosis, and autophagy. Variants in the usherin gene (USH2A) have been reported in autosomal recessive RP with or without hearing loss. In the present study, we aimed to identify causative variants in a Han-Chinese pedigree with autosomal recessive RP.

Methods: A six-member, three-generation Han-Chinese family with autosomal recessive RP was recruited. A full clinical examination, whole exome …

An Updated Examination Of The Perception Of Barriers For Pharmacogenomics Implementation And The Usefulness Of Drug/Gene Pairs In Latin America And The Caribbean, Aimeé Salas-Hernández, Macarena Galleguillos, Matías Carrasco, Andrés López-Cortés, María Ana Redal, Dora Fonseca-Mendoza, Patricia Esperón, Farith González-Martínez, Ismael Lares-Asseff, Alberto Lazarowski, Verónica Loera-Castañeda, Diadelis Remírez, Matías F Martínez, Rodrigo Vargas, Fabricio Rios-Santos, Antonio Macho, Juan P Cayún, Germán R Perez, Carolina Gutierrez, Leslie C Cerpa, Tamara Leiva, Susan Calfunao, Lesly Xajil, Christopher Sandoval, Marcelo Suárez, Ariana Gonzalez, Gabriela Echeverría-Garcés, Luis Sullón-Dextre, Eugenia Cordero-García, Alexis R Morales, Andrea Avendaño, Enrique Sánchez, Laura C Bastone, Cesar Lara, Patricia Zuluaga-Arias, Ana María Soler, Julio Da Luz, Gabriela Burgueño-Rodríguez, Marcelo Vital, Elizabeth Reyes-Reyes, Alexander Huaccha, Yeimy V Ariza, Naomi Tzul, Ana L Rendón, Roberto Serrano, Larissa Acosta, Angelo Motta-Pardo, Leonardo Beltrán-Angarita, Erika Brand, Miguel A Jiménez, Gladys Maribel Hidalgo-Lozada, Marina M J Romero-Prado, Karla Escobar-Castro, Mariel Umaña-Rivas, Juan D Vivas, Paola Lagos, Yineth Ballén Martínez, Sharleth Quesada, Camila Calfio, Maria L Arias, María A Lavanderos, Dante D Cáceres, Alberto Salazar-Granara, Nelson M Varela, Luis A Quiñones

Faculty, Staff and Student Publications

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers …

Disrupted Ca2+ Homeostasis And Immunodeficiency In Patients With Functional Ip3 Receptor Subtype 3 Defects, Julika Neumann, Erika Van Nieuwenhove, Lara E Terry, Frederik Staels, Taylor R Knebel, Kirsten Welkenhuyzen, Kourosh Ahmadzadeh, Mariah R Baker, Margaux Gerbaux, Mathijs Willemsen, John S Barber, Irina I Serysheva, Liesbeth De Waele, François Vermeulen, Susan Schlenner, Isabelle Meyts, David I Yule, Geert Bultynck, Rik Schrijvers, Stephanie Humblet-Baron, Adrian Liston

Faculty, Staff and Student Publications

Calcium signaling is essential for lymphocyte activation, with genetic disruptions of store-operated calcium (Ca2+) entry resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP3R), a homo- or heterotetramer of the IP3R1-3 isoforms, amplifies lymphocyte signaling by releasing Ca2+ from endoplasmic reticulum stores following antigen stimulation. Although knockout of all IP3R isoforms in mice causes immunodeficiency, the seeming redundancy of the isoforms is thought to explain the absence of variants in human immunodeficiency. In this study, we identified compound heterozygous variants of ITPR3 (a gene encoding IP3R subtype 3) in two unrelated Caucasian patients presenting with immunodeficiency. To determine whether ITPR3 …

Sustained Increases In Immune Transcripts And Immune Cell Trafficking During The Recovery Of Experimental Brain Ischemia, Munish Saini, Eshan Sengupta, Madanjit Singh, Harnoor Singh, Jaswinder Singh

Faculty, Staff and Student Publications

Sustainable Development Goals (SDG) are at the forefront of government initiatives across the world. The SDGs are primarily concerned with promoting sustainable growth via ensuring wellbeing, economic growth, environmental legislation, and academic advancement. One of the most prominent goals of the SDG is to provide learners with high-quality education (SDG 4). This paper aims to look at the perspectives of the Sustainable Development Goals improvised to provide quality education. We also analyze the existing state of multiple initiatives implemented by the Indian government in the pathway to achieving objectives of quality education (SDG 4). Additionally, a case study is considered …

Conformational Rearrangements In The Sensory Rcsf/Omp Complex Mediate Signal Transduction Across The Bacterial Cell Envelope, Sarah R Lach, Santosh Kumar, Seonghoon Kim, Wonpil Im, Anna Konovalova

Faculty, Staff and Student Publications

Timely detection and repair of envelope damage are paramount for bacterial survival. The Regulator of Capsule Synthesis (Rcs) stress response can transduce the stress signals across the multilayered gram-negative cell envelope to regulate gene expression in the cytoplasm. Previous studies defined the overall pathway, which begins with the sensory lipoprotein RcsF interacting with several outer membrane proteins (OMPs). RcsF can also interact with the periplasmic domain of the negative regulator IgaA, derepressing the downstream RcsCDB phosphorelay. However, how the RcsF/IgaA interaction is regulated at the molecular level to activate the signaling in response to stress remains poorly understood. In this …

A Bayesian Piecewise Exponential Phase Ii Design For Monitoring A Time-To-Event Endpoint, Yun Qing, Peter F Thall, Ying Yuan

Faculty, Staff and Student Publications

A robust Bayesian design is presented for a single-arm phase II trial with an early stopping rule to monitor a time to event endpoint. The assumed model is a piecewise exponential distribution with non-informative gamma priors on the hazard parameters in subintervals of a fixed follow up interval. As an additional comparator, we also define and evaluate a version of the design based on an assumed Weibull distribution. Except for the assumed models, the piecewise exponential and Weibull model based designs are identical to an established design that assumes an exponential event time distribution with an inverse gamma prior on …

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan

Faculty, Staff and Students Publications

PURPOSE: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.

METHODS: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.

RESULTS: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by …

Editorial: Insights In Neurogenomics: 2022, Aayushi Gandhi, Sarah H Elsea

Faculty, Staff and Students Publications

No abstract provided.

Community Engagement In Precision Medicine Research: Organizational Practices And Their Impacts For Equity, Janet K Shim, Nicole Foti, Emily Vasquez, Stephanie M Fullerton, Michael Bentz, Melanie Jeske, Sandra Soo-Jin Lee

Center for Medical Ethics and Health Policy Staff Publications

Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal.

Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for.

Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. …

Social Behavioral Impairments In Syngap1-Related Intellectual Disability, Hajer Naveed, Maria Mccormack, J Lloyd Holder

Duncan NRI Faculty and Staff Publications

Introduction: Developmental synaptopathies are neurodevelopmental disorders caused by genetic mutations disrupting the development and function of neuronal synapses.

Methods: We administered the validated Social Responsiveness Scale, Second Edition (SRS-2) to investigate the phenotypic presentation of social-behavioral impairments for the developmental synaptopathy-SYNGAP1-related Intellectual Disability (SYNGAP1-ID) (n = 32) compared with a phenotypically similar disorder Phelan-McDermid syndrome (PMD) (n = 27) and healthy controls (n = 43). A short form SRS-2 analysis (n = 85) was also conducted.

Results: Both SYNGAP1-ID and PMD had significantly elevated total and subcategory T-scores, with no significant score differences between SYNGAP1 …

Focused Ultrasound Thalamotomy: Correlation Of Postoperative Imaging With Neuropathological Findings, Sarah E Blitz, Matthew Torre, Melissa M J Chua, Sarah L Christie, Nathan J Mcdannold, G Rees Cosgrove

Duncan NRI Faculty and Staff Publications

Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is a rapidly developing technique used for tremor relief in tremor-predominant Parkinson's disease (PD) and essential tremor that has demonstrated successful results. Here, we describe the neuropathological findings in a woman who died from a fall 10 days after successful MRgFUS for tremor-predominant PD. Histological analysis demonstrates the characteristic early postoperative MRI findings including 3 distinct zones on T2-weighted imaging: (1) a hypointense core, (2) a hyperintense region with hypointense rim, and (3) a slightly hyperintense, poorly marginated surrounding area. Histopathological analyses also demonstrate the suspected cellular processes composing each of these regions including …

Initial Insights Into The Genetic Variation Associated With Metformin Treatment Failure In Youth With Type 2 Diabetes, Shylaja Srinivasan, Ling Chen, Miriam Udler, Jennifer Todd, Megan M Kelsey, Morey W Haymond, Silva Arslanian, Philip Zeitler, Rose Gubitosi-Klug, Kristen J Nadeau, Katherine Kutney, Neil H White, Josephine H Li, James A Perry, Varinderpal Kaur, Laura Brenner, Josep M Mercader, Adem Dawed, Ewan R Pearson, Sook-Wah Yee, Kathleen M Giacomini, Toni Pollin, Jose C Florez

Faculty, Staff and Students Publications

Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10−6), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P …

Public Mental Health During And After The Sars-Cov-2 Pandemic: Opportunities For Intervention, Melissa M Karnaze, Brent M Kious, Lindsay Z Feuerman, Sarah Classen, Jill O Robinson, Cinnamon S Bloss, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Importance: During the pandemic, the number of United States adults reporting clinically significant symptoms of anxiety and depression sky-rocketed, up from 11% in 2020 to more than 40% in 2021. Our current mental healthcare system cannot adequately accommodate the current crisis; it is therefore important to identify opportunities for public mental health interventions.

Objective: Assess whether modifiable emotional factors may offer a point of intervention for the mental health crisis.

Design setting and participants: From January 13 to 15, 2022, adults living in the United States were recruited via Amazon Mechanical Turk to complete an anonymous survey.

Main outcomes and …

Renewed Calls For Abortion-Related Research In The Post-Roe Era, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

Optimizing Human Performance In Extreme Environments Through Precision Medicine: From Spaceflight To High-Performance Operations On Earth, Michael A Schmidt, Jeffrey A Jones, Christopher E Mason

Faculty, Staff and Students Publications

Humans operating in extreme environments often conduct their operations at the edges of the limits of human performance. Sometimes, they are required to push these limits to previously unattained levels. As a result, their margins for error in execution are much smaller than that found in the general public. These same small margins for error that impact execution may also impact risk, safety, health, and even survival. Thus, humans operating in extreme environments have a need for greater refinement in their preparation, training, fitness, and medical care. Precision medicine (PM) is uniquely suited to address the needs of those engaged …

Tissue-Specific Dna Methylation Variability And Its Potential Clinical Value, Ryan H Miller, Chad A Pollard, Kristin R Brogaard, Andrew C Olson, Ryan C Barney, Larry I Lipshultz, Erica B Johnstone, Yetunde O Ibrahim, James M Hotaling, Enrique F Schisterman, Sunni L Mumford, Kenneth I Aston, Tim G Jenkins

Faculty, Staff and Students Publications

Complex diseases have multifactorial etiologies making actionable diagnostic biomarkers difficult to identify. Diagnostic research must expand beyond single or a handful of genetic or epigenetic targets for complex disease and explore a broader system of biological pathways. With the objective to develop a diagnostic tool designed to analyze a comprehensive network of epigenetic profiles in complex diseases, we used publicly available DNA methylation data from over 2,400 samples representing 20 cell types and various diseases. This tool, rather than detecting differentially methylated regions at specific genes, measures the intra-individual methylation variability within gene promoters to identify global shifts away from …

Ai-Powered Discovery Of A Novel P53-Y220c Reactivator, Shan Zhou, Dafei Chai, Xu Wang, Praveen Neeli, Xinfang Yu, Aram Davtyan, Ken Young, Yong Li

Faculty, Staff and Students Publications

Introduction

The p53-Y220C mutation is one of the most common mutations that play a major role in cancer progression.

Methods

In this study, we applied artificial intelligence (AI)-powered virtual screening to identify small-molecule compounds that specifically restore the wild-type p53 conformation from p53-Y220C. From 10 million compounds, the AI algorithm selected a chemically diverse set of 83 high-scoring hits, which were subjected to several experimental assays using cell lines with different p53 mutations.

Results

We identified one compound, H3, that preferentially killed cells with the p53-Y220C mutation compared to cells with other p53 mutations. H3 increased the amount of folded …

Tanshinone Iia Inhibits Cell Viability And Promotes Puma-Mediated Apoptosis Of Oral Squamous Cell Carcinoma, Shuangze Han, Xinfang Yu, Ruirui Wang, Xiaocong Wang, Lulu Liu, Qing Zhao, Rongbo Xie, Ming Li, Zhong Su Zhou

Faculty, Staff and Students Publications

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and …

Gene Expression Profiles In Cancers And Their Therapeutic Implications, Chad J Creighton

Faculty, Staff and Students Publications

The vast amount of gene expression profiling data of bulk tumors and cell lines available in the public domain represents a tremendous resource. For any major cancer type, expression data can identify molecular subtypes, predict patient outcome, identify markers of therapeutic response, determine the functional consequences of somatic mutation, and elucidate the biology of metastatic and advanced cancers. This review provides a broad overview of gene expression profiling in cancer (which may include transcriptome and proteome levels) and the types of findings made using these data. This review also provides specific examples of accessing public cancer gene expression data sets …

The Neurobiology Of Duration Of Untreated Psychosis: A Comprehensive Review, Anthony W Zoghbi, Jeffrey A Lieberman, Ragy R Girgis

Faculty, Staff and Students Publications

Duration of untreated psychosis (DUP) is defined as the time from the onset of psychotic symptoms until the first treatment. Studies have shown that longer DUP is associated with poorer response rates to antipsychotic medications and impaired cognition, yet the neurobiologic correlates of DUP are poorly understood. Moreover, it has been hypothesized that untreated psychosis may be neurotoxic. Here, we conducted a comprehensive review of studies that have examined the neurobiology of DUP. Specifically, we included studies that evaluated DUP using a range of neurobiologic and imaging techniques and identified 83 articles that met inclusion and exclusion criteria. Overall, 27 …