Sickle Cell Anemia

The inherited condition known as sickle cell disease (SCD) affects 2.6% of Americans, primarily those of African, Hispanic or Mediterranean descent but also individuals from the Middle East and Asia.

Overview

Named for the shape of patients’ red blood cells (RBCs), sickle cell disease is cause by a mutant form of hemoglobin makes RBCs become crescent-shaped and rigid, rather than round and pliant like normal RBCs. Circulating “sickled” RBCs stick together and impede blood flow. Since oxygen carried by any RBC is essential for life, oxygen deficiencies associated with SCD damage tissues and cause anemia, infection, and bouts of intense pain called vaso-occlusive crises. Current treatments cannot prevent these episodes or long-term organ damage that is even seen in infants and children with SCD. Patients typically do not live beyond their early 50s, with pulmonary dysfunction the most common cause of death.

LJI’s Joel Linden, Ph.D., is an expert on a group of anti-inflammatory cell surface proteins called adenosine receptors. Linden previously explored how the small molecule adenosine, which activates these receptors, protects tissues in the heart from damage due to low blood flow. Realizing that SCD patients also exhibit low blood flow, Linden reasoned that treatments that would activate adenosine receptors might ameliorate pain associated with that condition.

Linden began testing his theory in mouse models of SCD about four years ago and found that treatment with adenosine-like compounds countered the damaging effects of the disease. He was aware of an existing FDA-approved adenosine-like drug was already been approved for another use, meaning it was safe in humans and could probably gain rapid approval if proven effective in clinical trials as a treatment for sickle cell disease.

As a result, he and collaborators at Rady Children’s Hospital-San Diego are now in the midst of a phase 2 clinical trial of an adenosine-based anti-inflammatory agent as treatment for SCD’s severest pain symptoms.

In parallel, Linden’s lab is examining tissue damage that occurs after blood flow blockage in SCD is relieved. At that point, rapid restoration of normal blood flow can actually damage tissues (a condition called ischemia reperfusion injury), in part because it mobilizes immune cells known as natural killer T cells (NKTs), which mistake the body’s normal tissue for foreign invaders. Over a patient’s lifetime, multiple cycles of inappropriate NKT cell activation gradually worsen SCD lesions and potentially shorten that individual’s lifespan.

Linden thinks that many of the anti-inflammatory effects of adenosine are actually due to their ability to inhibit NKT cells. Thus, he is pursuing two new SCD treatments based on activation of adenosine and is seeking new opportunities to develop novel therapeutic approaches through adenosine receptors.

FACULTY MEMBERS

Amnon Altman, Ph.D.
Mitchell Kronenberg, Ph.D.
Stephen Wilson, Ph.D.
Brandon Fabritzky
Nunzio Bottini, M.D., Ph.D.
Hilde Cheroutre, Ph.D.
Michael Croft, Ph.D.
Toshiaki Kawakami, M.D., Ph.D.
Klaus Ley, M.D.
Yun-Cai Liu, Ph.D.
Catherine “Lynn” Hedrick, Ph.D.
Patrick Hogan, Ph.D.
Anjana Rao, Ph.D.
Matthias von Herrath, M.D.
Dirk Zajonc, Ph.D.
Joel Linden, Ph.D.
Stephen Schoenberger, Ph.D.
Sonia Sharma, Ph.D.
Alessandro Sette, Dr. Biol.Sci.
Bjoern Peters, Ph.D.
Chris Benedict, Ph.D.
Shane Crotty, Ph.D.
Sujan Shresta, Ph.D.
Jason Greenbaum, Ph. D.
Dave Hall
John E. Keegan
Cheryl Kim
Aaron Ling
Morag Mackay
Zbigniew Mikulski, Ph.D.
Margaret (Ng Thow) Hing, J.D.
Michael Scarpelli
Sue Son
John Stillwagen
John E. Major, Eng.D. h.c.
Richard S. Bodman
Anthony ”Tony” Carr
Leroy Hood, M.D., Ph. D.
Toshifumi Mikayama, Ph.D.
Gail Naughton, Ph.D., MBA
David Perkins
Hunt Pettit
Larry Spitcaufsky
David Dominguez
Robert C. Dynes, Ph.D.
David R. Webb, Ph.D.
Eric V. Zwisler
David Brenner, M.D.
Phillippa Marrack, Ph.D.
Kenneth Murphy, M.D., Ph.D.
Luise Sternberg, Ph.D.
Jian Sun
Joyce Chen
Romain Georges
Xiang Li
Chan-Wang (Jerry) Lio
Isaac Lopez-Moyado
Xiaojing Yue
Milad Bahmanof
Aaron Miller, MD, PhD
Leslie Montero, M.D.
Gabriele Foos
April Frazier, Ph.D.
Cecilia Lindestam Arlehamn, Ph.D.
Erin Moore
John Pham
Nima Salimi
Deborah Shackelford
John Sidney
Randi Vita, M.D.
Daniela Weiskopf
Leora Zalman, Ph.D.
Mariko Hara
Ann Balancio
Jiji Xie, Ph.D.
Rachid El Morabiti
Gaëlle Picarda
Stephanie Stanford, Ph.D.
Eugenio Santelli, Ph.D.
Cristiano Sacchetti, Ph.D.
Christian Secchi, Ph.D.
Alex Funderburk, B.S
Vida Zhang, B.S.
Caila Pilo, B.S.
Nathaniel Harder, B.S.
Hitoshi Iwaya, Ph.D.
Chris Lena
Yiran Wang-Zhu
Annie Elong Ngono, Ph.D.
Aruna Bitra, Ph.D.
Ricardo Da Silva Antunes, Ph.D.
Rana Herro
Amit Kumar Mehta, Ph.D.
Gina Kirchweger, Ph. D.
Ferhat Ay, Ph.D.
Simon Belanger
Jennifer Dan
Runpei (Amy) Wu
Debbi Yoakum
Yanfan (Peipei) Zhu
Yuko Kawakami
Zhichao Fan, Ph.D.
Kouji Kobiyama
Alex Marki, M.D.
Jacqueline Miller, B.Sc
Dennis Wolf, MD
Mark Bowles
Barton J. Cohen
Kris Charton
Gabriela Aguila
Ericka Castillo
Natalie von Herrath
Aparna Gudlur, Ph.D.
Nupura Hirve
Chen Zhang
Christian Elly
Jee Ho Lee, Ph.D.
Pandurangan Vijayanand, M.D. Ph.D.
Benjamin Schmiedel, Ph.D.
Greg Seumois
Anusha Preethi Ganesan
Colleen Barefield, PhD
Erin Randolph
Don Newmeyer, Ph.D.
Nicholas Thiault
Julie Burel, Ph.D.
Alba Grifoni, Ph.D.
Ward Fleri, Ph.D., PMP
Jose Regla Nava
Jihye Han
Clinical Coordinator
Hsin-Yu Liu
Abhijit Chakraborty, Ph.D.
Shilpi Verma
Kiyokazu Kakugawa
Robert Abbott
Jinyong Choi
Yu Kawakami
Shilpi Chandra
Catherine Crosby
Isaac Engel
Archana Khurana
Venetia C Morris
Masako Murai
Gooyoung Seo
Meng Zhao, Ph.D.
Yuan Lin
An Chi Mei
Tomomi Kuwana
Kenneth Chan
Sara McArdle, Ph.D.
Rafi Ahmed, Ph.D.
Raima Gosh
Randi Vita, M.D.
Diana Stillwagen
Shu Liang
Mary Jean Sunshine
Robert Signer
Arya Kaul
Ariel Madrigal
Vipul Shukla, Ph.D.
Ian Mathews
Young Jun Kang
Jeong Hyun (JH) Lee
Christopher Dillingham
Zachary Katz
Holger Winkels
Chris Surh
Tom Tullie
Chris Lee, MBA
Kelsey Dale
Eileen Timken
Ana Eliza Zeraik
Ravindra Gujar, Ph.D.
Aarthi Venkat
Zeynep Kosaloglu-Yalcin
Emilie Branche
Michael D. Coit
Robert W. Mahley, M.D., Ph.D.
Greet Verstichel, M.D., Ph.D.
Wade Zhang
Yu “Alex” Kato
Francois Ferré, Ph.D.
Lindsey Padgett
Mallory Paynich
Christine Bender, Ph.D.
Bharat Panwar
Katia Faliti, Ph.D.
Sourya Bhattacharyya, Ph.D.
Vanessa Wertheim, Ph.D.
Ying-Ting Wang
Lai Wen
Angeline Chen
Atsushi Onodera
Marco Orecchioni, Ph.D.
Steve Hedrick
Ciro Ramirez Suastegui
Huy Dinh, Ph.D.
Yingcong Li
Teodora Vozdolska
Xiaocui He
Claire Olingy
Vivek Chandra
Haruka Miki, Ph.D.
Praveen Akuthota
Stephen C. Pappas, J.D.
Yun Min Jung
Martin Naradikian
Quinn Bui
Leen Baudewijn
Miriama Kruta
Payal Ramchandani
Sara Herrera de la Mata
Jenna Hambrick
Angela Frentzen
Simon Eschweiler
Catherine Nakao
Pamela Wasserman, MPH
Rukman Thota
Rebecca Kuan
Payel Roy
Alice Wang
Spencer Brightman
Martina Dicker
Tiffany Chu
Nadine Hartmann and Angeliki Tsangaratou
Geneviève Tremblay Jacobs
Mercylia Susantono
Sanjana Balagere
Sakthi Rajendran
Yanal Ghosheh
Andrew Gonzalez
Hyungseok Seo
Austin Crinklaw
Amal Ali
Tom Riffelmacher, Ph.D.
Ryan Griswold
Erik Ehinger
Edahi Gonzalez Avalos
Chelsea Luedeke
Aaron Sutherland
Ramya Sreeramoju
Hugo Sepulveda
Massimo Bottini
Lynda Stuart, M.D., Ph.D.
Sandor W. Shapery, J.D.
Mitsuo Satoh, Ph.D.
Melissa Meyer
Chen Li
Jason Bennett
Joan Valls Cuevas
Mario Cabero Manresa
Jose Barrera
Bernadette Anne Chua
Estefania Quesada Masachs, M.D., Ph.D.
Jacquelyn Truong
Antonio Lanzaveccia, M.D.
Cornelis Murre (ad hoc), Ph.D.
Kit Durant
Mehdi Ayech Benkahla, Ph.D.
William B. Kiosses, Ph.D.
Paul Rubiro
Paul Kim
Akul Singhania
Rinkesh Gupta
Hannah Voic
Gabriel Ascui-Gac
Ferran Soldevila Casals, Ph.D.
Ting-Fang Chou
Noa Macdonald
Paramita Dutta
Erik Ehinger & Yanal Ghosheh
Zhen Dong
Angelica Becker
Bruce Beutler, M.D.
Andrew Hosogai
Cheryl Andreoli
Gregory Golden
Carolyn Moderbacher
Jamie Kwak
Roberta Nowak
Summer Khan
Susanne Pfeiffer
Ivy Phung
Hayley Simon
Stephanie Fotsing
Ryosuke Saigusa
Rashmi Tippalagama
Erica Ollmann Saphire, Ph.D.
Daniela Samaniego Castruita
Annie Vu
Malak Jaljuli
Kate Hastie
Camille Lenzi
Amar Parvate
Ruben Diaz Avalos
Samuel Zilberman
Le Zou
Andrea Roman
Diptiben Parekh
Tierra Buck
Christine Huh
Jenifer Vallejo
Simon Braumann
Monalisa Mondal
Bharat Panwar, Ph.D.
Sabrina Wu
Niu Du
Kenneth Kim, Ph.D.
Mike Norris
Haoyang Li
Liam King
Adrian Enriquez
Elaine Eng
Marshall Lammers
Timothy Lee
Jenny Lee
Kruti Patel
Nikhill Joshi
Katherine Dao
Matthew Busse
Lindy Edwards
Sean Hui
Xiaoying Yu
Jingru Fang
Sharon Schendel
Michelle Zandonatti
Andrew Saphire
Ingrid Stuiver, Ph.D.
Emilia Arturo, Ph.D.
Jen Li Salie
Heather Callaway
Anthony Kusnadi, Ph.D.
Sara Landeras Bueno, Ph.D.
Eric Johnson
Lorenzo Quiambao
Sengjun Park, Ph.D.
Kelly Shaffer
Joaquin Reyna
Yutaka Terada
Hal Wasserman
Stephanie Harkins
Timothy Baffi
Mason Lee
Chao Yang
Julia Timis
Jose Mateus Trivino
Benjamin Meckiff, Ph.D.
Paige Dubelko
Sophia Schreiber
Cristian Gonzalez-Colin
Vicente Fajardo Rosas
Jeffrey Wang
Michelle Moss
Jessica Jang
Ava Wittenberg
Ella Crotty
Maria Mesina
Allison Bien
Henry Madany
Rekha Dawani, Ph.D.
Jane Buckner, M.D.
Marc Jenkins, Ph.D.
Michael Dollar, CPA, CGMA
Alyssa Agarwal
Jessica Jou
Simon Brunel
Brian Freeman
Ana Almonte
Mehak Kaur
Vamseedhar Rayaprolu
Roshan Ahmed
Ikuo Takazawa
Payal Ramchandani
Senta Walton
Daniel Araujo
Rishab Gulati
Heena Mistry, Ph.D.
Brian Reardon
Andrew Wilson
Careers
Paul Thiel
Hwan Soo Kim
Srijan Chakraborty
Jeffrey Makings
Kristen Valentine
Yunliang Yao
Ahmed Azhan
Paul Zierep
Zeli Zhang
Yulia Kushnareva
Lulu Chea
Eric Tran
Christina Kim
James Clarke
Juan Carlos Castelan Angel
Shreyank Kadadi
Steve Zhang
Adrian von Witzleben
James Quinn
Jacob Doering-Powell
Matias Lin
Hao Wang
William Chronister
Brian Do
Maheshi Mapalagamage
Esther Dawen Yu
Artem Romanov
Myungja Ro
Gurupreet Sethi
Alexandra Tankka
Kennis-Grace Mrotek
Donglim Park
Zhe Zhu
Megan Lee
Hannah Hillman
Jeffrey Morgan
Jiani Chai
Jieyun Yin
Denise Beckmann
Chitra Hariharan
Evelien Bunnik
Anna-Sophia Dinov
João Rodrigues
Abbas Roayaei Ardakany
Storrey Lance
Matthew Dykstra
Shankari Mylvaganam
Amabel Lopez-Rodriguez
Rory de Vries
Pramod Shinde
Daniel Marrama
Maëva Hervieu
Tong Jin
Richard Harris
Hui Zhi
Dansen Wu
Sara Yanke
Hannah Cluster
Wanchen Hsieh
Martina Zoccheddu
Shen Yang
Justin Cayford
David M. Rickey
J. Mark Waxman
Alex Moon-Walker
Julia Zhou
Christopher Romano
Zhihao Wang
Subbareddy Duvuuru

From The Lab

Jun 12, 2013

New Sickle Cell Anemia Therapy advances to Phase II Clinical Trials