Jian  Lu,  Ph. D

 Department of Molecular Biology and Genetics               

Cornell University

 227 Biotechnology Building                                              

Ithaca, NY, 14850, USA      


Email:          JL2434@cornell.edu


Telephone:   (607) 255-1707                                             

Short Biography

      I am a postdoc associate in Dr. Andrew Clark’s lab at the Department of Molecular Biology and Genetics, Cornell University.   I received my B.S. and M.S. degrees in Cellular Biology and Genetics from Peking University in 1999 and 2002, respectively.   I earned my Ph.D. degree in Ecology and Evolution in 2008 from University of Chicago under the guidance of Dr. Chung-I Wu. My research focuses on gene regulatory networks mediated by microRNAs and other classes of small RNAs

Research Interests

       A central goal in modern biology is to understand how gene regulatory networks function to maintain biological robustness and how changes in the regulatory networks contribute to phenotypic variations and diseases. To pursue this question, I am combining my expertise in Computational Biology, Evolutionary Genomics and RNA Biology to i) identify novel genetic changes, ii) study their impacts on fitness and phenotypes, and iii) understand the evolutionary forces driving these processes.   Although my interest has spanned a wide range of aspects of gene regulation, my   current research focuses on the variation and evolution of small RNA targeting. 

       Gene regulation mediated by microRNA targeting is a burgeoning topic.  MicoRNAs are a class of small noncoding RNAs (~22 nts) that regulate expression of target genes at the post-transcriptional level.  SiRNAs (20-22 nts) and piRNAs (26-30 nts) are two other classes of small RNAs.  In Drosophila, they are mainly involved in defense against invasion of viruses or transposable elements, although they can also regulate gene expression.  The three classes of small RNAs are distinct in both functional mechanisms and expression patterns, but they share similarities in target recognition because the key RISC components (Argonaute proteins) in the three pathways are homologous. 

       In my Ph. D. study under the supervision of Dr. Chung-I Wu, my colleagues and I deep-sequenced microRNAs from three species of Drosophila.  I observed a large class of microRNA genes that are evolutionarily young.  I proposed that most of the newly emerged microRNAs are evolutionarily transient and undergo a rapid birth and death process.  Only a small fraction of the newly emerged microRNAs eventually become functionally integrated into the regulatory networks (Lu et al. 2008b).    By comparing the divergence and polymorphism of four newly emerged microRNA genes that have survived in the genome for more than 50 million years, we inferred that these new microRNAs have undergone a long period of adaptive evolution before functional integration (Lu et al. 2008a; Tang et al. 2010).

       In 2008, I joined Dr. Andrew Clark's lab at Cornell University as a postdoc associate.   I have been employing next generation sequencing techniques coupling with comparative genomics and population genetics modeling to study functions of microRNAs in diverse biological processes:  (1) The regulatory effects of microRNAs in innate immunity of Drosophila; (2) The impacts of microRNA regulation on natural variation in human gene expression; and (3) Function of microRNAs in human cancer progression.  We have identified a large number of microRNAs and mRNAs with expression profiles changed during these biological processes.   The ongoing analyses are to investigate the regulatory impacts of microRNAs on the target genes in the contexts of regulatory networks.

    In the future I will continue to use Drosophila and human as models to study the variation and evolution of gene expression regulation mediated by small RNAs both within populations and at the inter-species divergence level.  I will acombine pproaches of computational, comparative and functional genomics ith evolutionary theory and population genetics modeling.  The ultimate goal of my future research is to understand how gene expression architecture evolves to cause variation in phenotypic traits, reproductive isolation, adaptation to environments, and diseases. 

      Besides the projects of small RNA targeting, during my Ph. D. training, I extensively combined computational biology, functional genomics and population genetics modeling to explore evolutionary dynamics of protein coding genes in human (Lu et al. 2003; Lu and Wu 2005) and in rice (Lu et al. 2006; Tang et al. 2006).  The projects are summarized as below. 

      (1) Fixation of slightly deleterious mutations in the naturally–occurring species. The nearly neutral theory of molecular evolution (Ohta,1973) argued that the neutral theory (Kimura, 1968) should be extended to include random fixation of very slightly deleterious mutations.  If the nearly neutral theory holds true, how much of the molecular divergence between closely related species might be contributed by slightly deleterious mutations?  By comparing the evolutionary rates of X chromosome vs. autosomes between human and chimpanzee, we concluded that at least 90% of the synonymous substitutions are deleterious but the fitness effect is weaker than the effect of genetic drift (Lu&Wu, 2005).  This project reveals that extensive slight deleterious mutations are fixed in the naturally–occurring species. 

      (2) Fixation of deleterious mutations in the domesticated species. Due to the inbreeding effect, the domesticated species behave like asexual species because effective recombination is greatly reduced.  Therefore, deleterious mutations will not be removed efficiently by purifying selection since the efficacy of purifying selection is reduced due to the Hill Robertson(1966) effect.  By comparing 4,000 orthologous genes across the two subspecies ((japonica and indica)) of the domesticated rice, Oryza Sativa and the wild rice O. brachyantha, I estimated that about 25% of the amino acid changes are deleterious but persist in the genomes of domesticated rice due to the Hill Robertson effect under domestication. (Lu et al. 2006). By surveying genetic variation patterns in rice cultivars and wild rice species, as part of a joint collaboration, I found extensive alleles introgressed from wild rice to cultivars, which might contribute to the enormous range of phenotypic variation observed among domesticated breeds (Tang et al. 2006).

    Besides the aforementioned projects, I cooperated with Dr. Hua Tang on evolutionary index analyses (Tang et al. 2004), Dr. Josh Shapiro on adaptive genic evolution in Drosophila (Shapiro et al. 2007),  Dr. HurngYi Wang on evolution of gene expression(Wang et al. 2008), and Dr. Andrew Clark and colleagues on the evolutionary genomics of the 12 Drosophila genomes (Clark et al. 2007).



03/2008  Ph.D.   Ecology and Evolution, the University of Chicago

   Thesis Advisor: Dr. Chung-I Wu

07/2002  M.S.      Genetics, Peking University, China

   Thesis Advisor : Prof. Zhuohua Dai

07/1999  B.S.     Cell Biology and Genetics, Peking University, China        

Academic Appointments

06/2008-current,   Advisor: Dr. Andrew G. Clark

Postdoctoral Research Associate, Department of Molecular Biology and Genetics, Cornell University 

Research focus:  regulatory impacts of microRNAs on innate immunity of Drosophila, on natural variation in gene expression, and on cancer progression; evolution and functional genomics of piRNAs and siRNAs.

04/2008-05/2008,   Advisor: Dr. Chung-I Wu  

Postdoctoral Research Associate, Department of Ecology and Evolution, the University of Chicago

09/2002-03/2008,   Advisor: Dr. Chung-I Wu

Research Assistant, Department of Ecology and Evolution, the University of Chicago

Research focus: population genetics and evolutionary genomics of protein coding genes; the origin and subsequent evolution of microRNAs.


Publications (Peer-Reviewed Articles) 

1. Lu J, Clark AG (2010)

A pilot study on microRNAs in innate immunity of Drosophla (in preparation).

2. Lu J, Li M, Clark AG, Yu XQ (2010)

The role of microRNAs in progression of human renal cell carcinoma as revealed by ultradeep next-generation sequencing (in preparation).

3. Lu J, Clark AG (2010)

Impact of microRNA regulation on variation in human gene expression (Under review at Genome Research).

4. Lu J, Clark AG (2010)

Wide-spread regulatory effects of endogenously expressed siRNAs on the  transcriptomes of Drosophila melanogaster (Ready for submission).

5.  Zhou RC, Ling SP, Zhao WM, Osada N, Chen SF, Zhang M, He ZW, Bao H, Zhong CR, Zhang B, Lu XM, Turissini D, Duke NC, Lu J, Shi SH, Wu CI (2010)

Population genetics in non-model organisms: II Natural selection in marginal habitats revealed by deep sequencing on dual platforms. (Under review at Molecular Biology and Evolution, Lu J is a co-corresponding author).

6.  Tang T, Kumar S, Shen Y, Lu J, Wu ML, Shi S, Li WH, Wu CI (2010)

Adverse interactions between micro-RNAs and target genes from different species.

Proceedings of the National Academy of Sciences 107: 12935-12940.

7.  Lu J, Clark AG (2010)

Population dynamics of PIWI-interacting RNAs (piRNAs) and their targets in Drosophila. Genome Research 20: 212-227.

8.  Lu J, Shen Y,Wu QF, Kumar S, He B, Carthew RW, Wang SM, Wu CI (2008)

The birth and death of microRNA genes in Drosophila. 

Nature Genetics 40: 351-355; author reply in 42: 9-10.  

9.   Lu J, Fu Y, Kumar S, Shen Y, Zeng K, Xu A, Carthew RW, Wu CI (2008)

Adaptive evolution of newly emerged micro-RNA genes in Drosophila.

Molecular Biology and Evolution 25: 929-938.

10. Wang HY, Fu Y, McPeek MS, Lu X, Nuzhdin S, Xu A, Lu J, Wu ML, Wu CI (2008) Complex genetic interactions underlying expression differences between Drosophila races: analysis of chromosome substitutions.

Proceedings of the National Academy of Sciences 105: 6362-6367.

11. Wu QF, Kim YC, Lu J, Xuan ZY, Chen J, Zheng YL, Zhou T, Zhang MQ, Wu CI, Wang SM (2008)  

Poly A- Transcripts Expressed in HeLa Cells. 

PLoS ONE 3(7): e2803.

12.  Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA et al (2007) Evolution of genes and genomes on the Drosophila phylogeny.

Nature 450: 203-218 (Lu J is a coauthor of this paper).

13. Shapiro JA, Huang W, Zhang C, Hubisz MJ, Lu J, Turissini DA, Fang S, Wang HY, Hudson RR, Nielsen R, Chen Z, Wu CI (2007)

Adaptive Genic Evolution in the Drosophila Genomes.

Proceedings of the National Academy of Sciences 104: 2271-2276.

14.  Lu J, Tang T, Tang H, Huang JZ, Shi SH, Wu CI (2006)

The accumulation of deleterious mutations in rice genomes: a hypothesis on the cost of domestication.

Trends in Genetics 22: 126-131 (Lu J and Tang T equally contribute to the paper).

 15. Tang T, Lu J, Huang J, He J, McCouch SR, Purugganan MD, Shi SH, Wu CI (2006)  

Genomic variation in rice - Genesis of highly polymorphic linkage blocks during domestication.

PLoS Genetics 2(11):e199 (Tang T and Lu J equally contribute to the paper).  

16. Lu J, Wu CI (2005) 

Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee.

Proceedings of the National Academy of Sciences 102: 4063-4067.

17. Tang H, Wyckoff GJ, Lu J, Wu CI (2004)

A universal evolutionary index for amino acid changes.

Molecular Biology and Evolution 21: 1548-1556.

18. Lu J, Li WH, Wu CI (2003)

Comment on "Chromosomal speciation and molecular divergence-accelerated evolution in rearranged chromosomes".

Science  302: 988.

19. Lu J, Lü J, Chen HX, Zhang WX, Dai ZH (2002)

Molecular phylogeny of Drosophila auraria species complex (in Chinese).

Acta Genetica Sinica 29: 39-49.

20. Zhao Z, Lu J, Dai ZH (2001)

Genetic differentiation within Drosophila auraria species complex revealed by Random Amplified Polymorphic DNA (RAPD) (in Chinese).

Acta Zool. Sinica 47: 625-631.


Grant Application

I was actively involved in the following grant application:

(1) the National Institute of Health (NIH, 5R01AI064950-05)

“Functional and comparative genomic of Drosophila immunity”. 

PI: Dr. Andrew G. Clark

(2) the National Institute of Health (NIH, 5R01GM058686-09)

“MicroRNA evolution and species divergence”.   

PI: Dr. Chung-I Wu

(3) the Chicago Biomedical Consortium’s Catalyst Award

Functions and Evolution of micro-RNAs”.   

PI: Drs. Richard Carthew, San Ming Wang & Chung-I Wu

(4)  National Natural Science Foundation, China (Key project, 30730008)

“Mechanisms of adaptation and speciation at the genomic level in mangroves of the intertidal zones”.  

PI: Dr. Shi, Suhua



Honors, Awards and Fellowships

2008    Honorable Mention for Best Dissertation of Division of Biological Sciences, 

        the University of Chicago

 2007   Chinese government award for outstanding self-financed students   

        abroad(5,000 US dollars)

2006    Hutchinson Charles L. & Kinsley, France s/Botany Department Fund 

        (9,116 US dollars)

2000   Guangcai Scholarship of Peking University (500 US dollars) 

Presentations & Invited Talk

1. Lu J, Clark AG [oral presentation]

Impact of microRNA regulation on variation in human gene expression.

The Summer 2010 Post-doc Seminar Series, Department of Molecular Biology and Genetics, Cornell University, August, 2010.


2. Lu J, Clark AG [oral presentation]

Population dynamics of PIWI-interacting RNAs (piRNAs) and their targets in Drosophila. 51st Annual Drosophila Research Conference, Washington DC, April, 2010.


3. Lu J, Clark AG [oral presentation]

Evolutionary and functional genomics of small RNAs in Drosophila.

The Summer 2009 Post-doc Seminar Series, Department of Molecular Biology and Genetics, Cornell University, August, 2009.


4. Lu J, Shen Y,Wu QF, Kumar S, He B, Carthew RW, Wang SM, Wu CI [poster]

The birth and death of microRNA genes in Drosophila. 

50th Annual Drosophila Research Conference, Chicago, IL, March, 2009.


5. Lu J, Wu CI [poster]

Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee.

The Biology of Genomes, Cold Spring Harbor, May, 2005.


6. Lu J, Wu CI [departmental seminar]

Genetic costs during rice domestication.

Sun Yat-Sen University, Guangzhou, China, July, 2005. 


Teaching Experience

2011        2-day course on microRNA regulation

Sun Yat-Sen University, China (to be scheduled)


2010      2-day course on Population Genetics and Molecular Evolution

Peking University, China (to be scheduled)


2003     Teaching assistant with Dr. Chung-I Wu for Population Genetics,

the University of Chicago


2001    Teaching assistant with Prof. Zhuohua Dai for Genetics & Genetics Lab,

Peking University, China



Society for Molecular Biology and Evolution  

American Association for the Advancement of Science

Sigma Xi Society


Peer Reviewer for

Genome Research, Molecular Biology and Evolution, Genome Biology and Evolution,  Journal of Molecular  Evolution, PLoS Computational Biology, PLoS ONE, Gene



Jian Lu,
Feb 2, 2010, 6:49 PM