Research projects

Our laboratory explores the physiological role of (a) endoplasmic reticulum (ER) homeostasis and (b) inflammatory responses in the context of metabolic disorders including obesity, type-1/-2 diabetes and inflammatory bowel disease. Our goal is to uncover new findings, break new grounds, delineate the etiology and pathogenesis of human diseases, and eventually help develop therapeutic strategies. In the past 7 years, using cellular, immunological and molecular biology approaches, we have made some important discoveries and produced new insights into the pathogenesis of these diseases. Our studies have provided important insights into the pathogenesis of various diseases, especially metabolic syndromes such as obesity, type-1 and -2 diabetes, neonatal diabetes or mutant insulin-gene-induced diabetes of youth (MIDY), and inflammatory bowel disease (IBD).  Certain important themes have emerged from our studies. To keep this summary brief, I have highlighted two central themes.


A defining feature of any physiological process is the recurring nature and balance of the signaling circuits and in the case of endoplasmic reticulum (ER), is the dynamic control of protein folding and degradation.  Using animal models, we have investigated how the cell maintains ER homeostasis.  First, we have pioneered novel methods to quantitate the level of stress in the ER by quantitating the percent of IRE1a phosphorylation, the key ER stress sensor (Cell Metabolism 2009).  This discovery has solved a long-standing challenge in the field of ER biology and has transformed the field into a quantifiable science.  This method also allows us and others to quantitatively measure the level of ER stress under various physiological and pathological conditions (Developmental Cell 2012, Diabetes 2014) and reveal important insights into the role of ER homeostasis in health and disease.  Second, we have revealed, for the first time, the physiological and pathological significance of ER-associated degradation (ERAD) in cell type-specific manner in diverse physiological contexts (PNAS 2014; Cell Metabolism 2014; Nat Cell Biol 2015; Mol Biol Cell 2016).  We were the first to demonstrate Sel1L as an indispensable component of Hrd1 ERAD complex in mammals in vivo, discover novel links between Sel1L-Hrd1 ERAD and a number of disease-associated proteins and pathways including IRE1a and lipoprotein lipase.  These studies have delineated physiological and pathological importance of ERAD, identified several endogenous misfolding-prone ERAD substrates and established a common theme of ERAD dysfunction in the pathogenesis of various seemingly distinct diseases.  Our achievements build on our desire to think outside the box, take the risk and develop breakthrough science.

We are at the forefront of physiological ER stress and ERAD field to delineate the role of ERAD in vivo, with a special focus on the most conserved Sel1L-Hrd1 protein complex in health and disease.  Specifically, we will delineate cell type-specific ERAD in various cell types in vivo, and reveal pathophysiological significance of the ERAD system in the pathogenesis of various diseases including immunodeficiency, diabetes, obesity and neurodegeneration.  We are uniquely positioned because of many Sel1L-Hrd1 ERAD deficient cell and mouse models that we have recently generated, because of our innovative spirits, passion and dedication to scientific discovery and because of our diverse research expertise in many different areas.  By systemically identifying cell type-specific ERAD substrates in distinct physiological contexts, we may transform the field from a rough description to a series of molecular details of (patho-)physiological importance of ERAD in diverse physiological contexts.  Our work will reveal the elaborate orchestrations of ER protein folding and ERAD that lie at the heart of normal cellular function and physiology.

We will tackle many intriguing questions in the field, in particularly, (a) how different cell types including hepatocytes, adipocytes (both white and brown), intestinal epithelia, pancreatic β cells, B cells, neurons and etc deal with protein misfolding and manage ER homeostasis under various disease settings in vivo, (b) how ERAD is linked to other signaling pathways and nutrient metabolism in vivo, and (c) biochemically how ER homeostasis is regulated in the cell as well as the nature of endogenous ERAD substrates. These studies will likely have significant impact as they will fundamentally change our views on the role of ER homeostasis, ERAD and protein folding and degradation in physiology and diseases.

Studies in this area have been funded by two NIDDK R01s, one NIGMS R01, NIAAA R21, ADA Career Developmental Award. Studies have been published in Nat Cell Biol, Cell Metabolism, Developmental Cell, Diabetes, PNAS, Mol Biol Cell and J Biol Chem. 


A long-standing puzzle of the “immunometabolism” field is how the low-grade inflammation is initiated and maintained in obesity. Our goal is to identify immune populations that are important to counter the proinflammatory effect of HFD and obesity. We demonstrated that myeloid-derived suppressor cells (MDSCs) are involved in immunoregulation in WAT by acting as immunosuppressors (J Biol Chem 2011). We recently discovered a critical role of NKT cells in adipose inflammation and type-2 diabetes. To dissect primary events associated with obesity, we investigated events at 4 day HFD where we found that NKT cells are activated and regulate macrophage polarization and glucose tolerance via IL-4.  Among all the publications on adipose NKT, we were the first one to report that NKT cells act as a lipid sensor to link HFD feeding and inflammatory responses in WAT (J Biol Chem 2012a; 2012b). Recently, we showed a dispensable role of ATP-P2X7 signaling axis in inflammasome activation in obese adipose tissue (Diabetes 2012).  Lastly, while investigating the role of TLR signaling pathways in inflammation, we serendipitously observed that TLR2/4 double knockout mice die from lethal pulmonary damage following chronic HFD feeding, which is associated with changes in gut microbiota (Cell Reports 2014).

For future studies, we will continue investigating how and when inflammation is initiated with a special focus on β cells, and how inflammatory signals control β cell proliferation. We believe that our recent study has unlock the secrets of β cell proliferation in adults.

Studies in this area have been funded by NIDDK R01, ADA Junior Faculty Award, JDRF Innovative Award and Strategic Research Agreement and others. Studies have been published in Cell Metabolism, Diabetes, J Biol Chem, Cell Reports, Endocrinology, and etc. 

Lab in the News

11/12/15    Cornell Chronicle      Mechanism underlying cell stress response discovered  (

8/4/14    Cornell Chronicle      A new player in lipid metabolism discovered (

6/18/14    Cornell Chronicle     Chronic intake of Western diet kills mice  (

5/28/14    Cornell Chronicle     20 Cornellians win SUNY Chancellor’s Awards for Excellence (

1/22/14    Cornell Chronicle     Gene prevents buildup of misfolded cell proteins  (

 8/21/13       ABC News        There’s no perfect diet, researcher says  (

5/13             Diabetes Forecast       Powering Diabetes Research (with a profile of Dr. Ling Qi) (

12/20/12    Cornell Chronicle    Researchers link protein known for cell mobility with protein folding during stress  (

5/7/12        Cornell Chronicle    Immune cells found to counter obesity-related diabetes (

3/14/12      Cornell Daily Sun    The Scientist: Prof. Ling Qi Examines Fat Cell Responses to Obesity and Diabetes  (

1/31/12      Cornell Chronicle    Qi wins prestigious American Diabetes Association award (

8/17/11      Cornell Chronicle    Grad student wins Hughes fellowship for doctoral research (

 6/2/09       Cornell Chronicle      Cornell researchers discover key regulator of fat cell development   (

6/5/08       Cornell Chronicle       Cornell researcher strives to break the link between obesity and diabetes   (